Sie sind auf Seite 1von 13

Indian Journal of Experimental Biology

Vol. 47, October 2009, pp. 779-791

Review Article

Comparative genomic hybridization array study and its utility in detection of


constitutional and acquired anomalies
Joris Andrieux & Frenny Sheth*
Laboratory of Medical Genetics, Jeanne de Flandre Hospital CHRU de Lille, Lille Cedex, France

The last decade has witnessed an upsurge in the knowledge of cytogenetic disorders and putting the old technology in a
new basket with molecular genetics. As conventional cytogenetic can detect the genetic alteration of 10-15 Mb, many of the
micro-deletions and micro-duplications are missed. However, with the advent of technology of fluorescence in situ
hybridization (FISH), the resolution of genetic aberrations can reach to 3-5 Mb, nonetheless the anomalies smaller than the
above, need further precision which has been achieved using comparative genomic hybridization array (CGH-array).
Introduction of array-CGH has brought higher sensitivity with automated DNA fragment analyzer and DNA chip for
submicroscopic chromosomal anomalies that are missed till date in many of the acquired and constitutional genetic
disorders. The resolution of the technology varies from several Kb to 1 Mb depending upon the type of array selected. With
the recent improvement in the array-CGH technology, a link between cytogenetic and molecular biology has been
established without replacing conventional cytogenetic technique. The wider accessibility of the technology shall certainly
provide a clue to the many unidentified/unexplained genetic disorders which shall prove to be a boon to the clinicians.

Keywords: Acquired anomalies, Array-CGH, Constitutional disorders, Molecular karyotyping

Cytogenetic study has remained the clinicians’ Table 1—Landmark in the history of conventional cytogenetic
favorite for many of the genetic disorders especially and molecular cytogenetic
in unexplained psychomotor retardation [with/without Year Discovery Ref.
dysmorphism], abnormality of sexual differentiation 1
1959 First Chromosomal anomaly Lejune J
and development, infertility, recurrent pregnancy loss, detected [Trisomy 21]
pregnancy at risk for aneuploidy, chromosome 1969 Molecular hybridization of Pardue & Gall2
breakage syndrome and cancer. However, limitation radioactive DNA to the DNA of
of band resolution has added the plethora of research cytological preparations
studies in search for technology that can visualize 1976 High resolution banding Yunis3
chromosomal anomalies which are thought to be not technique
existing or missed. This has transformed cytogenetics 1981 Isotopic in situ hybridization Harper & Saunders4
to the molecular cytogenetics with an unmatched 1984 Direct FISH Landegent5
precision and knowledge gained so far. Though 1986 Interphase FISH Cremer et al6 & Pinkel
et al7
chromosomal abnormalities remain a major cause of
1989 Combinatorial labeling Nederlof et al8
most of the genetic disorders, limitations of high 1989 Primed in situ hybridization Koch et al9
resolution, missed many of the genetic disorders [PRINS]
while molecular biology has its limitations of known 1990 Identification of translocation in Tkachuk et al10
targeted anomalies identification. These limitations Interphase cell by FISH
have transformed the newer innovation with high end 1990 Technique of ratio labeling Nederlof et al11
precision of cytogenetic techniques (Table 1). 1992 Comparative Genomic Kallioniemi et al12
Nonetheless all these technology have their limitation Hybridization [CGH]
that uses comprehensive analysis of the disorders 1993 Fiber FISH Parra & Windle13
—————— 1996 Multiplex FISH [M-FISH] Speicher et al14
*Correspondent author’s present address: 1996 SKY Schrock et al15
FRIGE (Foundation for Research in Genetics and Endocrinology), 1997 Cross species color Banding Muller et al16
Institute of Human Genetics, FRIGE House, Jodhpur Road, [Rx FISH]
Satellite, Ahmedabad 380 015, India 1997 DNA array (matrix) CGH Solinas-Toldo17
Telephone: 079-26921414
1997 Padlock probe FISH Nilsson et al18
Fax: 079-26921415
E-mail: frennysheth@hotmail.com 1998 Array CGH using BAC clones Pinkel et al19
780 INDIAN J EXP BIOL, OCTOBER 2009

using cytogenetics to molecular cytogenetics to Molecular biology allows precise analysis of


array—comparative genomic hybridization (CGH). variations at the nucleotide level. Molecular
Table 2 shows comparison of each technology, its cytogenetic techniques, mainly Fluorescence in situ
uses and limitations for understanding genomic hybridization (FISH), which is currently useful on
imbalances in various genetic disorders. both metaphase chromosomes and interphase cells,
utilize genomic sequence-probes in bacterial
Techniques and levels of resolution artificial chromosome [BAC 100-200 kb] cloned in
Conventional cytogenetic [CC] technique, the Escherichia coli or P1 artificial chromosome [PAC
standard karyotype (400-bands per haploid genome) 100-150 kb] cloned in phage. These sequences are
allows a level of resolution, from 10-15 Mb (million tagged with fluorochrome, which allows the
base pairs). In the best conditions, the high-resolution detection of genomic imbalances involving
karyotype (550-bands) allows to reveal anomalies of chromosome segments smaller than 1 Mb for
about 3 to 5 Mb according to the regions of the deletions and more than 2 Mb for duplications. This
genome and the technique used (G-bands, R-bands). technique is more useful to detect micro-deletion and
The limitation of enhance resolution of the karyotype alteration at the telomeric region, which are not
is not only linked to the cytogenetic technique used (it identifiable with conventional cytogenetics (CC).
is possible to get karyotypes up to 850-bands), but This can be confirmed and correlated with the
also the region of interest. clinical symptoms. It is important to know that this
Secondly, the cytogenetic technique is only partly technique can identify only the specific region of the
automated; need insight, indebt knowledge and interest [specific sequence used as probe] and not the
experience of the cytogeneticists. whole genome in a single assay.
Table 2—Comparison of technical details between conventional cytogenetic and major molecular approaches
Method Analysis Resolution Applications Limitation

Conventional Cell culturing: Whole genome 10-15 Mb Detection of balance and unbalance Minor rearrangements
cytogenetics arresting cell in defects cannot be detected
metaphase
High resolution arresting cell in Whole genome 3-5 Mb Detection of balance and unbalance Micro-deletions and
banding technique metaphase defects terminal aberrations can
not be detected.
Conventional Molecular Identify 1-3 Mb Detect all types of balanced and Structural anomalies
FISH biology specific region Metaphase unbalanced defects in metaphase, cannot be detected in non-
technique interphase cell, frozen section and dividing cells. Smaller
50 Kb dead cells. FISH is highly sensitive
Interphase cells for trisomy than
monosomy
Spectral arresting cell in Whole genome 1-2 Mb Detect numerical and structural Inability to detect
Karyoytping/ M- metaphase aberrations including subtle paracentromeric inversion,
FISH rearrangements, complex small deletion/duplications
translocation, small marker, ring and cryptic translocation
and double minute chromosomes in
a single experiments with all 24
chromosomes
CGH Molecular Whole genome 3-5 Mb No need for cell culture or Cannot detect Balanced
biology technique metaphase, does not require fresh translocation, gain/loss of
sample, frozen or fixed sample can <4 Mb, multiplication of
be used, interpretation of highly 2n
complex karyotype with accurate
chromosomal location of imbalance
Array-CGH Molecular Whole genome 20 - 150 Kb Specifications are same as above. Cannot detect balanced
biology technique Can identify cryptic translocation, mosaicism
rearrangements, More sensitive and less than 50%, and
can be use for both quantitative heterochromatic region
genomic imbalance and gene
expression as well
ANDRIEUX & SHETH : CGH-ARRAY STUDY & ITS UTILITIES 781

Another molecular technique to analyse pange- quantities of DNA from the patient and control are
nomic alteration is CGH on metaphase. Here test labelled with different fluorochromes and hybridized
DNA (patient) and reference DNA (normal on a glass slide coated with an ordered set of defined
individual) are differentially labeled with two nucleic acid sequences17. This technological
fluorescence dyes and co-hybridized on metaphase development allows screening of large number of
spreads of a normal individual. A copy number genomic DNA sequences in a single experiment,
difference between test DNA and reference DNA will depending on the size of the spotlength of DNA
be reflected in fluorescence ratio. These ratios of [60bp]. Chromosomal imbalances across the genome
fluorochromes are visualised under microscope using can be mapped and quantified by analyzing the
appropriate filters and analysed with the aid of fluorescence ratio of the two dyes for each target.
software that discern genome structure variation DNA quantitative variation can be identified, only if
[deletion, duplication, amplifications, monosomies, the DNA fragments used on the glass slide covers
trisomies etc.] present in the DNA of the patient. This regions of interest.
technique has an advantage of identifying anomalies Technological progress accomplished in the last
in segments, which are not identified by G- or R- years, allow spotting of more than a million fragments
banding technique. Secondly, DNA of the test subject of DNA. Particularly for pangenomic studies, the
is used for the processing and hybridizes on the resolution depends on the number of DNA probes
normal male metaphase hence culturing of the cells spotted on the coated glass and the resolution is very
are not required. This is mainly useful in cases of close to few kilobases. This has made possible several
prenatal, onco-hematological and in tumor cases as applications such as whole chromosome studies20, a
well. One of the limits of CGH on chromosomes, in chromosome segment21, all sub-telomeric regions22, or
addition to poor reproducibility is its level of entire genome with a 1Mb resolution ranging from
resolution, which does not exceed 3-5 Mb [similar to (classical BACs/PACs array) to 10-100kb
high-resolution banding] (Fig. 1). (oligonucleotide array). Hence, this is going to
Recent advancements in array-CGH has made it provide the “connecting link” between cytogenetic
possible to substitute the chromosome target with and molecular biology for quantitative detection of
DNA spotted on a glass slide. The processing structural variation at genomic level. The term of
technique is similar to that of CGH metaphase. Equal molecular karyotype is now closer to reality23,24.
Types of CGH-array
BAC/PAC arrays— The use of DNA from cosmid,
P1, BAC and other large insert clones as targets were
first shown by Pinkel et al19. 1 Mb resolution can be
achieved by using 3200-3500 clones covering the
entire genome. Using this array, many cryptic
polymorphisms have been detected. However, array-
CGH using BACs/PACs create difficulties to
differentiate between potentially pathogenic and poly-
morphisms as around 10% of the used clones are
polymorphic25. In addition presence of Common
Number Variations / Polymorphisms (CNV/CNP)
further confounds analysis.
Recently overlapping clones [tiling path array
using 32,433 clones]26 have been used which provide
resolution of ~200kb on average. These have higher
cost than the 3200-3500 but allows detection of more
number of variations.
Oligonucleotide array — Commercially available
array-CGH oligonucleotides are available with
Fig. 1—CGH on chromosome (http:// www.sanger.ac.uk/ HGP/ densities of clones from 15,000-1 million probes. This
Cytogenetics/) increases the resolution up to 20-30 kb on the entire
782 INDIAN J EXP BIOL, OCTOBER 2009

genome with an increased density in the coding micro-array was totally used to rule out genetic
region of the genome27. alterations in onco-haematological and tumor
Another approach is to use Single Nucleotide pathology until 2005 (Table 3).
Polymorphisms (SNP) micro-arrays, which allow In this domain, detection of quantitative genomic
detection of partial/complete disomies28 when finding alterations was linked to tumor progression and its
losses of heterozygosity (LOH) without quantitative therapeutic approach92. Various pathologies studied
DNA imbalances. are shown in Table 3.
Databases and bio-computer science—Data Though pathologies are secondary to the
processing plays a central role in interpretation. anomalies, it helps not only in the diagnosis but in the
Various softwares have been developed allowing to prognosis as well. There is specificity and limitations
process the data, to facilitate the interpretation using linked in CGH-Array applied to cancers and to
statistical algorithms and to generate a graph of the leukaemias are as follows:
results automatically. Nonetheless the interpretation Clonal anomalies: Different cell population (tumor
of these data is done only after studying whole and normal) are frequently observed in samples.
genome databases (Ensembl - Cambridge, UK-, Minor clone anomalies can easily be detected by CC
UCSC Genome Browser - Santa Cruz, USA) and as cell culture allows the immature cells to divide for
database of polymorphisms (Database of Genomic the analysis but in array-CGH, the DNA of normal
Variants, Toronto, Canada) (Fig. 2). cells is mixed with DNA from abnormal cell
population. Hence, abnormal clone if less than 30%,
Applications cannot be detected by array-CGH (Fig. 3).
Applications in onco-hematology and tumors— Sample preparation: Especially in solid tumor,
From the literature survey it can be noticed that CGH sometimes DNA is extracted from the fixed histo

Fig. 2—Interpretation of the data using whole genome databases


ANDRIEUX & SHETH : CGH-ARRAY STUDY & ITS UTILITIES 783

Table 3—Examples of onco-hematology and solid tumors studied pathological tissue that often generates poor quality
by array-CGH DNA leading to improper hybridization and inter-
Diseases Ref. pretation difficulties.
Acute myeloid leukemia, myelodysplasia 29-34 Patient data: Large number of patients DNA is
Acute lymphocytic leukemia 35-41 required for same clinical diagnosis to identify
Chronic myelogenous leukemia 42 recurrent anomalies by array-CGH.
Chronic lymphocytic leukemia 43,44 Applications in constitutional abnormalities— In
Lymphoma 45-50
term of diagnosis, array-CGH is particularly well
Multiple myeloma 51,52
Mesothelioma 53-55
suitable for the constitutional anomalies where they
Breast cancer 56-63 find, more often causative genetic alterations than in
Ovary cancer 64,65 onco-haematology and cancers, where they find
Colorectal adenocarcinoma 66-68 anomalies often consequence to the disease.
Liver cancer 69-71 • Application of array: CGH in constitutional genetic
Pancreatic cancer 72,73 is validation and measurement of the abnormality
Bladder cancer 74-76 detected by CC. Array-CGH is very useful to map
Prostate cancer 77-79
and measure precisely the size of the aberration
Neuroblastoma 80-83
Glioblastoma 84-86
using region specific arrays. CC analysis showed
Medulloblastoma 87,88 additional genetic material on #8p arm to a 3 yrs
Thyroid cancer 89,90 old female having MCA and developmental
Thymoma 91 delay [ 46, XX,add(8) † (8;?)(p23;?)]. Array - CGH

Fig. 3–Minor clones [~50%] cannot be detected by array-CGH


784 INDIAN J EXP BIOL, OCTOBER 2009

confirmed deletion of 8.3Mb on #8 and duplication as seen in Fig. 4c where duplication of 15q23q26.3
of 42.2 Mb of #15 leading to partial monosomy of involving IGF1R is associated with clinical
#8p and partial trisomy of #15q (Fig. 4 a-c). To features of macrocephaly, over growth and mental
date several chromosomal regions or whole retardation. Indeed high resolution array-CGH can
chromosomes were studied using tiling path or be successfully used to detect cryptic imbalances at
high-resolution array21. the chromosomal breakpoints97.
• To identify de novo marker chromosomes: measure • To rule out genomic alterations in clinically suspected
precisely gain and/or loss of chromosomal cases having normal chromosomal constitution25,97-106
segment, in a single assay (Fig. 5 a-b) 93-96 Since several years various international centres are
• In the vast majority of cases, apparently balanced actively involved for diagnosis in constitutional
structural chromosome abnormalities are not genetics using array-CGH and came to a conclusion
associated with an abnormal phenotype. However, that in cases of psychomotor delay/congenital
some carriers of apparently balanced de novo or malformation, when the results of CC are normal, the
inherited rearrangements present abnormal pick-up rate of interstitial micro-deletion/duplication
phenotypic features. The abnormal phenotype may after proper clinical history is around 2-3% using
be explained by the disruption of a gene, a high-resolution karyotype and additional 2-5% cases
positional effect or a cryptic genomic imbalance at are diagnosed using targeted telomeric region studies
the breakpoint or in another region of the genome (FISH or MLPA).

Fig. 4–(a): metaphase showing additional genetic material on #8p:46,XX,add(8) † (8;?)(p23;?) (b): Schematic representation shows
8p23.3p23.1 deletion of 8.3 Mb (c): Schematic representation shows 15q23q26.3 duplication of 42.2 Mb
ANDRIEUX & SHETH : CGH-ARRAY STUDY & ITS UTILITIES 785

Fig. 6–Potential of array-CGH in mental retardation

CGH-array can replace high resolution karyotyping


in confirming clinical diagnosis in the medium term
and the standard cytogenetics will always remain the
gold standard at the time of reference and the
anomalies detected by array-CGH will be further
validated using FISH analysis for deletions and
quantitative-PCR for duplications smaller than 2 Mb.

Limitations
• Although array-CGH has proved to be an efficient
and reproducible technique, there are some
limitations. Array-CGH could not easily
characterize the structural configuration of
balanced chromosomal anomalies. Particularly the
Fig. 5 – (a): Metaphase showing presence of marker chromosome order and orientation of the rearranged segments
[47,XX,+mar] (b): Schematic representation shows cannot be determined. Also, low-level mosaicism
18p11.332p11.31 duplication of 14.9 Mb (i.e. < 30%) may be difficult to detect.
Nonetheless, around 6-30% abnormities were • Structural alteration involving heterochromatic
detected using array- CGH after selecting various region cannot be detected. [unpublished data]
criteria such as cytogenetic interpretation, molecular • DNA of same sex is used as control in array-CGH,
analysis along with clinical sign and symptoms107-113. however in cases where the case subject is female
Array- CGH distinguishes on average 10-20% of having two X chromosomes and marker is of
anomaly in patients having psychomotor delay along Y origin, then this Y chromosome cannot be
with more or less congenital malformations. Deletion identified117.
is observed in two third and duplication in one third • The choice between the uses of BAC/PAC or
of the cases114. oligonucleotide array solely depends on the quality
The published results point out the potential of this of manufacture’s slides and designing of the
technology and its power concerning the detection of probes, reproducibility of the technology,
cryptic chromosomal alterations in cases having robustness of the developed statistical tool, analysis
mental retardation (Fig. 6)112,113,115,116. of the results and level of resolution. The choice of
786 INDIAN J EXP BIOL, OCTOBER 2009

technology is the result of comparison between 6 Cremer T, Landegent J, Bruckner A, Scholl H, Schardin M,
cost and resolution we expect. Hager H, Devilee P, Pearson P & Ploeg van der M, Detection
of chromosome aberrations in the human interphase nucleus
• Most of the false results (negative / positive) are by visualization of specific target DNAs with radioactive and
consequential from poor hybridization, linked to non-radioactive in situ hydridization techniques: Diagnosis
bad quality DNA or it is above recognizable of trisomy 18 with probe L1.84, Hum Genet, 74 (1986) 346.
threshold. 7 Pinkel D, Straume T & Gray J, Cytogenetic analysis using
quantitative, high-sensitivity, fluorescence hybridization,
• Last but not the least is the differentiation between Proc Natl Acad Sci U S A, 83 (1986) 2934.
real polymorphism and potentially pathogenic 8 Nederlof P, Robinson D, Abuknesha R, Wiegant J, Hopman
polymorphism as it is also present in a normal A, Tanke H & Raap A, Three-color fluorescence in situ
parent. Therefore, before applying array-CGH as a hybridization for the simultaneous detection of multiple
routine diagnostic tool, a better knowledge of these nucleic acid sequences, Cytometry, 10 (1989) 20.
polymorphisms is obligatory. 9 Koch JE, Kølvraa S, Petersen KB, Gregersen N & Bolund L,
Oligonucleotide-priming methods for the chromosome-
Conclusion specific labelling of alpha satellite DNA in situ,
Array-CGH allow testing a huge number of loci in Chromosoma, 98 (1989) 259.
10 Tkachuk DC, Westbrook CA, Andreeff M, Donlon TA,
one experiment and it is likely that it will replace
Cleary ML, Suryanarayan K, Homge M, Redner A, Gray J &
FISH approach to characterize deletion/duplication Pinkel D, Detection of bcr-abl fusion in chronic myelo-
breakpoints or to screen for known micro-deletion geneous leukemia by in situ hybridization, Science, 250
syndromes and sub-telomeric imbalances. Array-CGH (1990) 559.
is faster, has a better resolution, is a wonderful tool to 11 Nederlof PM, van der Flier S, Wiegant J, Raap AK, Tanke
screen pangenomic and constitutes the “Connecting HJ, Ploem JS & van der Ploeg M, Multiple fluorescence in
situ hybridization, Cytometry, 11 (1990) 126.
Link” between CC and molecular biology for the
12 Kallioniemi A, Kallioniemi O, Sudar D, Rutovitz D, Gray J,
detection of cryptic quantitative genomic alterations. Waldman F & Pinkel D, Comparative genomic hybridization
Array-CGH is still at a high cost and requires for molecular cytogenetic analysis of solid tumors, Science,
expensive apparatus for analysis and an expensive 258 (1992) 818.
technical environment, as well as a good level of 13 Parra I & Windle B, High resolution visual mapping of
expertise. This can be partly supplemented by the stretched DNA by fluorescent hybridization, Nat Genet, 5
(1993) 4.
choice of the appropriate array and its resolution in
14 Speicher M, Gwyn Ballard S & Ward D, Karyotyping human
the quantification (losses or gains) of the genomic chromosomes by combinatorial multi-fluor FISH, Nat Genet,
modifications. 12 (1996) 368.
15 Schröck E, du Manoir S, Veldman T, Schoell B, Wienberg J,
Acknowledgement Ferguson-Smith M, Ning Y, Ledbetter D, Bar-Am I,
This work was supported by UICC (International Soenksen D, Garini Y & Ried T, Multicolor spectral
Union against Cancer), Geneva, Switzerland and karyotyping of human chromosomes, Science, 273 (1996)
Department of Biotechnology, India (BT/PR/9111 494.
/MED/12/337/2007). Thanks are also due to Dr. 16 Müller S, Rocchi M, Ferguson-Smith M & Wienberg J,
Toward a multicolor chromosome bar code for the entire
Jayesh Sheth for comments. human karyotype by fluorescence in situ hybridization, Hum
Genet, 100 (1997) 271.
References
17 Solinas-Toldo S, Lampel S, Stilgenbauer S, Nickolenko J,
1 Lejeune J, Gautier M & Turpin R, Etude des chromosomes
Benner A, Dohner H, Cremer T & Lichter P, Matrix-based
somatiques de neuf enfants Mongolians, C R Acad Sci Paris,
comparative genomic hybridization: biochips to screen
248 (1959) 1721
for genomic imbalances, Genes Chromosome Cancer, 20
2 Pardue ML & Gall JG, Molecular hybridization of
(1997) 399.
radioactive DNA to the DNA of cytological preparations,
Proc Natl Acad Sci USA, 64 (1969) 600 18 Nilsson M, Krejci K, Koch J, Kwiatkowski M, Gustavsson P
3 Yunis J, High resolution of Human chromosome, Science, & Landegren U, Padlock probes reveal single-nucleotide
191 (1976) 1268. differences, parent of origin and in situ distribution of
4 Harper ME & Saunders GF, Localization of single copy centromeric sequences in human chromosomes 13 and 21,
DNA sequences on G banded human chromosomes by in situ Nat Genet, 16 (1997) 252.
hybridization, Chromosoma, 83 (1981) 431. 19 Pinkel D, Segraves R, Sudar D, Clark S, Poole I, Kowbel D,
5 Langent JE, Jansen in de Wal N &Baan R, 2- Collins C, Kuo W L, Chen C, Zhai Y, Dairkee S H, Ljung B
acetylaminofluorene modifide probes for the indirect M, Gray J W & Albertson D G, High resolution analysis of
hybridocytochemical detection of specific nucleic acid DNA copy number variation using comparative genomic
sequences, Exp Cell Res, 153 (1984) 61. hybridization to micro-arrays, Nat Genet, 20 (1998) 207.
ANDRIEUX & SHETH : CGH-ARRAY STUDY & ITS UTILITIES 787

20 Albertson D G, Ylstra B, Segraves R, Collins C, Dairkee S 32 Paulsson K, Heidenblad M, Strömbeck B, Staaf J, Jönsson G,
H, Kowbel D, Kuo W L, Gray J W & Pinkel D, Quantitative Borg A, Fioretos T & Johansson B, High-resolution genome-
mapping of amplicon structure by array CGH identifies wide array-based comparative genome hybridization reveals
CYP24 as a candidate oncogene, Nat Genet, 25(2) cryptic chromosome changes in AML and MDS cases with
(2000) 144. trisomy 8 as the sole cytogenetic aberration, Leukemia, 20
21 Maas N M, Van Buggenhout G, Hannes F, Thienpont B, (2006) 840.
Sanlaville D, Kok K, Midro A, Andrieux J, Anderlid B M, 33 Tyybäkinoja A, Saarinen-Pihkala U, Elonen E & Knuutila S,
Schoumans J, Hordijk R, Devriendt K, Fryns J P & Amplified, lost and fused genes in 11q23-25 amplicon in
Vermeesch J R, Genotype-phenotype correlation in 21 acute myeloid leukemia, an array-CGH study, Genes
patients with Wolf-Hirschhorn syndrome using high Chromosomes Cancer 45 (2006) 257.
resolution array comparative genome hybridization (CGH), 34 Martínez-Ramírez A, Urioste M, Melchor L, Blesa D, Valle
J Med Genet, 45(2) (2008) 71. L, de Andrés SA, Kok K, Calasanz MJ, Cigudosa JC &
22 Veltman J A, Schoenmakers E F, Eussen B H, Janssen I, Benítez J, Analysis of myelodysplastic syndromes with
Merkx G, van Cleef B, van Ravenswaaij C M, Brunner H G, complex karyotypes by high-resolution comparative genomic
Smeets D & Van Kessel A G, High-throughput analysis of hybridization and subtelomeric CGH array, Genes
subtelomeric chromosome rearrangements by use of array- Chromosomes Cancer 42 (2005) 287.
based comparative genomic hybridization, Am J Hum Genet, 35 Davidsson J, Andersson A, Paulsson K, Heidenblad M,
70 (2002) 1269. Isaksson M, Borg A, Heldrup J, Behrendtz M, Panagopoulos
23 Vermeesch J R, Melotte C, Froyen G, Van Vooren S, Dutta I, Fioretos T & Johansson B, Tiling resolution array
B, Maas N, Vermeulen S, Menten B, Speleman F, De Moor comparative genomic hybridization, expression and
B, Van Hummelen P, Marynen P, Fryns J P & Devriendt K, methylation analyses of dup(1q) in Burkitt lymphomas and
Molecular karyotyping: array CGH quality criteria for pediatric high hyperdiploid acute lymphoblastic leukemias
constitutional genetic diagnosis, J Histochem Cytochem, 53 reveal clustered near-centromeric breakpoints and
(2005)13. overexpression of genes in 1q22-32.3, Hum Mol Genet 16
24 Sanlaville D, Lapierre J M, Turleau C, Coquin A, Borck G, (2007) 2215.
Colleaux L, Vekemans M & Romana S P, Molecular 36 Clappier E, Cuccuini W, Kalota A, Crinquette A, Cayuela
karyotyping in human constitutional cytogenetics, Eur J Med JM, Dik WA, Langerak AW, Montpellier B, Nadel B,
Genet, 48 (2005) 214. Walrafen P, Delattre O, Aurias A, Leblanc T, Dombret H,
25 Andrieux J, Array-CGH for routine diagnosis of cryptic Gewirtz AM, Baruchel A, Sigaux F & Soulier J, The C-MYB
chromosomal imbalances, Pathol Biol 56 (2008) 368-74. locus is involved in chromosomal translocation and genomic
26 Ishkanian A S, Malloff C A, Watson S K, DeLeeuw R J, duplications in human T-cell acute leukemia (T-ALL), the
Chi B, Coe B P, Snijders A, Albertson D G, Pinkel D, Marra translocation defining a new T-ALL subtype in very young
M A, Ling V, MacAulay C & Lam W L, A tiling resolution children, Blood 110 (2007) 1251.
DNA microarray with complete coverage of the human 37 Kuchinskaya E, Nordgren A, Heyman M, Schoumans J,
genome, Nat Genet, 36(3) (2004) 299. Corcoran M, Staaf J, Borg A, Söderhäll S, Grandér D,
27 Barrett M T, Scheffer A, Ben-Dor A, Sampas N, Lipson D, Nordenskjöld M & Blennow E, Tiling-resolution array-CGH
Kincaid R, Tsang P, Curry B, Baird K, Meltzer P S, reveals the pattern of DNA copy number alterations in acute
Yakhini Z, Bruhn L & Laderman S, Comparative genomic lymphoblastic leukemia with 21q amplification: the result of
hybridization using oligonucleotide microarrays and total telomere dysfunction and breakage/fusion/breakage cycles,
genomic DNA, Proc Natl Acad Sci, 101 (2004)11765. Leukemia, 21 (2007) 1327.
28 Komura D, Shen F, Ishikawa S, Fitch K R, Chen W, Zhang J, 38 Schoumans J, Johansson B, Corcoran M, Kuchinskaya E,
Liu G, Ihara S, Nakamura H, Hurles M E, Lee C, Scherer S Golovleva I, Grandér D, Forestier E, Staaf J, Borg A,
W, Jones K W, Shapero M H, Huang J & Aburatani H, Gustafsson B, Blennow E & Nordgren A, Characterisation of
Genome-wide detection of human copy number variations dic(9;20)(p11-13;q11) in childhood B-cell precursor acute
using highdensity DNA oligonucleotide arrays, Genome Res, lymphoblastic leukaemia by tiling resolution array-based
16 (2006)1575. comparative genomic hybridisation reveals clustered
breakpoints at 9p13.2 and 20q11.2, Br J Haematol, 135
29 Suela J, Alvarez S & Cigudosa JC, DNA profiling by
(2006) 492.
arrayCGH in acute myeloid leukemia and myelodysplastic
syndromes, Cytogenet Genome Res, 118 (2007) 304. 39 Paulsson K, Heidenblad M, Mörse H, Borg A, Fioretos T &
Johansson B, Identification of cryptic aberrations and
30 Tyybäkinoja A, Elonen E, Piippo K, Porkka K & Knuutila S,
characterization of translocation breakpoints using array
Oligonucleotide array-CGH reveals cryptic gene copy
CGH in high hyperdiploid childhood acute lymphoblastic
number alterations in karyotypically normal acute myeloid
leukemia, Leukemia 20 (2006) 2002.
leukemia. Leukemia, 21 (2007) 571,
40 van Vlierberghe P, Meijerink JP, Lee C, Ferrando AA, Look
31 Rücker FG, Bullinger L, Schwaenen C, Lipka DB,
AT, van Wering ER, Beverloo HB, Aster JC & Pieters R, A
Wessendorf S, Fröhling S, Bentz M, Miller S, Scholl C,
new recurrent 9q34 duplication in pediatric T-cell acute
Schlenk RF, Radlwimmer B, Kestler HA, Pollack JR, Lichter
lymphoblastic leukemia, Leukemia, 20 (2006) 1245.
P, Döhner K & Döhner H, Disclosure of candidate genes in
acute myeloid leukemia with complex karyotypes using 41 Lilljebjörn H, Heidenblad M, Nilsson B, Lassen C, Horvat A,
microarray-based molecular characterization, J Clin Oncol, Heldrup J, Behrendtz M, Johansson B, Andersson A
24 (2006) 3887. & Fioretos T, Combined high-resolution array-based
788 INDIAN J EXP BIOL, OCTOBER 2009

comparative genomic hybridization and expression profiling 52 Largo C, Saéz B, Alvarez S, Suela J, Ferreira B, Blesa D,
of ETV6/RUNX1-positive acute lymphoblastic leukemias Prosper F, Calasanz MJ & Cigudosa JC, Multiple myeloma
reveal a high incidence of cryptic Xq duplications and primary cells show a highly rearranged unbalanced genome
identify several putative target genes within the commonly with amplifications and homozygous deletions irrespective of
gained region, Leukemia, 21 (2007) 2137. the presence of immunoglobulin-related chromosome
42 Hosoya N, Sanada M, Nannya Y, Nakazaki K, Wang L, translocations, Haematologica, 92 (2007) 795.
Hangaishi A, Kurokawa M, Chiba S & Ogawa S, 53 Lindholm PM, Salmenkivi K, Vauhkonen H, Nicholson AG,
Genomewide screening of DNA copy number changes in Anttila S, Kinnula VL & Knuutila S, Gene copy number
chronic myelogenous leukemia with the use of high- analysis in malignant pleural mesothelioma using
resolution array-based comparative genomic hybridization, oligonucleotide array CGH, Cytogenet Genome Res, 119
Genes Chromosomes Cancer, 45 (2006) 82. (2007) 119 46.
43 Patel A, Kang SH, Lennon PA, Li YF, Rao PN, Abruzzo L, 54 Zanazzi C, Hersmus R, Veltman IM, Gillis AJ, van Drunen
Shaw C, Chinault AC & Cheung SW, Validation of a E, Beverloo HB, Hegmans JP, Verweij M, Lambrecht BN,
targeted DNA microarray for clinical evaluation of recurrent Oosterhuis JW & Looijenga LH, Gene expression profiling
abnormalities in chronic lymphocytic leukemia, Am J and gene copy-number changes in malignant mesothelioma
Hematol 83 (2008) 540. cell lines, Genes Chromosomes Cancer, 46 (2007) 895.
44 Tyybakinoja A, Vilpo J & Knuutila S, High-resolution 55 Schulten HJ, Perske C, Thelen P, Polten A, Borst C,
oligonucleotide array-CGH pinpoints genes involved in Gunawan B & Nagel H, Establishment and characterization
cryptic losses in chronic lymphocytic leukemia, Cytogenet of two distinct malignant mesothelioma cell lines with
Genome Res 118 (2007) 8. common clonal origin, Cancer Genet Cytogenet, 176
45 Rubio-Moscardo F, Climent J, Siebert R, Piris MA, Martín- (2007) 35.
Subero JI, Nieländer I, Garcia-Conde J, Dyer MJ, Terol MJ, 56 Rouleau E, Lefol C, Tozlu S, Andrieu C, Guy C, Copigny F,
Pinkel D & Martinez-Climent JA, Mantle-cell lymphoma Nogues C, Bieche I & Lidereau R, High-resolution
genotypes identified with CGH to BAC microarrays define a oligonucleotide array-CGH applied to the detection and
leukemic subgroup of disease and predict patient outcome, characterization of large rearrangements in the hereditary
Blood, 105 (2005) 4445. breast cancer gene BRCA1, Clin Genet, 72 (2007) 199.
57 Melchor L, Honrado E, García MJ, Alvarez S, Palacios J,
46 Wessendorf S, Barth TF, Viardot A, Mueller A, Kestler HA,
Osorio A, Nathanson KL & Benítez J, Distinct genomic
Kohlhammer H, Lichter P, Bentz M, Döhner H, Möller P &
aberration patterns are found in familial breast cancer
Schwaenen C, Further delineation of chromosomal
associated with different immunohistochemical subtypes,
consensus regions in primary mediastinal B-cell lymphomas:
Oncogene 27 (2008) 3165.
an analysis of 37 tumor samples using high-resolution
58 Johnson N, Speirs V, Curtin NJ & Hall AG, A comparative
genomic profiling (array-CGH), Leukemia, 21 (2007) 2463.
study of genome-wide SNP, CGH microarray and protein
47 Kim WS, Honma K, Karnan S, Tagawa H, Kim YD, Oh YL, expression analysis to explore genotypic and phenotypic
Seto M & Ko YH, Genome-wide array-based comparative mechanisms of acquired antiestrogen resistance in breast
genomic hybridization of ocular marginal zone B cell cancer, Breast Cancer Res Treat 111 (2008) 55
lymphoma: comparison with pulmonary and nodal marginal 59 Climent J, Garcia JL, Mao JH, Arsuaga J & Perez-Losada J,
zone B cell lymphoma, Genes Chromosomes Cancer 46 Characterization of breast cancer by array comparative
(2007) 776. genomic hybridization, Biochem Cell Biol 85 (2007) 497.
48 Mestre-Escorihuela C, Rubio-Moscardo F, Richter JA, 60 Vincent-Salomon A, Gruel N, Lucchesi C, MacGrogan G,
Siebert R, Climent J, Fresquet V, Beltran E, Agirre X, Dendale R, Sigal-Zafrani B, Longy M, Raynal V, Pierron G,
Marugan I, Marín M, Rosenwald A, Sugimoto KJ, Wheat de Mascarel I, Taris C, Stoppa-Lyonnet D, Pierga JY,
LM, Karran EL, García JF, Sanchez L, Prosper F, Staudt Salmon R, Sastre-Garau X, Fourquet A, Delattre O, de
LM, Pinkel D, Dyer MJ & Martinez-Climent JA, Cremoux P & Aurias A, Identification of typical medullary
Homozygous deletions localize novel tumor suppressor breast carcinoma as a genomic sub-group of basal-like
genes in B-cell lymphomas, Blood, 109 (2007) 271. carcinomas, a heterogeneous new molecular entity, Breast
49 Fukuhara N, Tagawa H, Kameoka Y, Kasugai Y, Karnan S, Cancer Res, 9 (2007) R24.
Kameoka J, Sasaki T, Morishima Y, Nakamura S & Seto M, 61 Orsetti B, Nugoli M, Cervera N, Lasorsa L, Chuchana P,
Characterization of target genes at the 2p15-16 amplicon in Rougé C, Ursule L, Nguyen C, Bibeau F, Rodriguez C &
diffuse large B-cell lymphoma, Cancer Sci, 97 ( 2006) 499. Theillet C, Genetic profiling of chromosome 1 in breast
50 Chen W, Houldsworth J, Olshen AB, Nanjangud G, Chaganti cancer: mapping of regions of gains and losses and
S, Venkatraman ES, Halaas J, Teruya-Feldstein J, Zelenetz identification of candidate genes on 1q, Br J Cancer, 95
AD & Chaganti RS, Array comparative genomic (2006) 1439.
hybridization reveals genomic copy number changes 62 Bergamaschi A, Kim YH, Wang P, Sørlie T, Hernandez-
associated with outcome in diffuse large B-cell lymphomas, Boussard T, Lonning PE, Tibshirani R, Børresen-Dale AL &
Blood, 107 (2006) 2477. Pollack JR, Distinct patterns of DNA copy number alteration
51 Largo C, Alvarez S, Saez B, Blesa D, Martin-Subero JI, are associated with different clinicopathological features
González-García I, Brieva JA, Dopazo J, Siebert R, Calasanz and gene-expression subtypes of breast cancer, Genes
MJ & Cigudosa JC, Identification of overexpressed genes in Chromosomes Cancer, 45 (2006) 1033.
frequently gained/amplified chromosome regions in multiple 63 van Beers EH & Nederlof PM, Array-CGH and breast
myeloma, Haematologica, 91 (2006) 184. cancer, Breast Cancer Res, 8 (2006) 210.
ANDRIEUX & SHETH : CGH-ARRAY STUDY & ITS UTILITIES 789

64 Nowee ME, Snijders AM, Rockx DA, de Wit RM, Kosma schistosomiasis-associated bladder cancers by using array
VM, Hämäläinen K, Schouten JP, Verheijen RH, van Diest comparative genomic hybridization analysis? Cancer Genet
PJ, Albertson DG & Dorsman JC, DNA profiling of primary Cytogenet, 177 (2007) 153.
serous ovarian and fallopian tube carcinomas with array 76 Blaveri E, Brewer JL, Roydasgupta R, Fridlyand J, DeVries
comparative genomic hybridization and multiplex ligation- S, Koppie T, Pejavar S, Mehta K, Carroll P, Simko JP &
dependent probe amplification, J Pathol, 213 (2007) 46. Waldman FM, Bladder cancer stage and outcome by array-
65 Mayr D, Kanitz V, Anderegg B, Luthardt B, Engel J, Löhrs based comparative genomic hybridization, Clin Cancer Res,
U, Amann G & Diebold J, Analysis of gene amplification 11 (2005) 7012.
and prognostic markers in ovarian cancer using comparative 77 Lapointe J, Li C, Giacomini CP, Salari K, Huang S, Wang P,
genomic hybridization for microarrays and immunohisto- Ferrari M, Hernandez-Boussard T, Brooks JD & Pollack JR,
chemical analysis for tissue microarrays, Am J Clin Pathol, Genomic profiling reveals alternative genetic pathways of
126 (2006) 101. prostate tumorigenesis, Cancer Res, 67 (2007) 8504.
66 Fijneman RJ, Carvalho B, Postma C, Mongera S, van 78 Paris PL, Sridharan S, Scheffer A, Tsalenko A, Bruhn L &
Hinsbergh VW & Meijer GA, Loss of 1p36, gain of 8q24, Collins C, High resolution oligonucleotide CGH using DNA
and loss of 9q34 are associated with stroma percentage of from archived prostate tissue, Prostate, 67 (2007) 1447.
colorectal cancer, Cancer Lett, 258 (2007) 223. 79 Sun J, Liu W, Adams TS, Sun J, Li X, Turner AR, Chang B,
67 Fensterer H, Radlwimmer B, Sträter J, Buchholz M, Aust Kim JW, Zheng SL, Isaacs WB & Xu J, DNA copy number
DE, Julié C, Radvanyi F, Nordlinger B, Belluco C, Van alterations in prostate cancers: a combined analysis of
Cutsem E, Köhne CH, Kestler HA, Schwaenen C, Nessling published CGH studies, Prostate, 67 (2007) 692.
M, Lutz MP, Lichter P, Gress TM & EORTC 80 Stallings RL, Origin and functional significance of large-
Gastrointestinal (GI) Group, Matrix-comparative genomic scale chromosomal imbalances in neuroblastoma, Cytogenet
hybridization from multicenter formalin-fixed paraffin- Genome Res, 118 (2007) 110.
embedded colorectal cancer tissue blocks, BMC Cancer, 7 81 Do JH, Kim IS, Park TK & Choi DK, Genome-wide
(2007) 58. examination of chromosomal aberrations in neuroblastoma
68 Lassmann S, Weis R, Makowiec F, Roth J, Danciu M, Hopt SH-SY5Y cells by array-based comparative genomic
U & Werner M, Array CGH identifies distinct DNA copy hybridization, Mol Cells, 24 (2007) 105.
number profiles of oncogenes and tumor suppressor genes in 82 Scaruffi P, Coco S, Cifuentes F, Albino D, Nair M,
chromosomal- and microsatellite-unstable sporadic colorectal Defferrari R, Mazzocco K & Tonini GP, Identification and
carcinomas, J Mol Med, 85 (2007) 293. characterization of DNA imbalances in neuroblastoma by
69 Sun B, Wu J, Zhang T & Wang C, High-resolution analysis high-resolution oligonucleotide array comparative genomic
of genomic profiles of hepatocellular carcinoma cells with hybridization, Cancer Genet Cytogenet, 177 (2007) 20.
differential osteopontin expression, Cancer Biol Ther 83 Mosse YP, Diskin SJ, Wasserman N, Rinaldi K, Attiyeh EF,
7 (2008) 387 Cole K, Jagannathan J, Bhambhani K, Winter C & Maris JM,
70 Steinemann D, Skawran B, Becker T, Tauscher M, Neuroblastomas have distinct genomic DNA profiles that
Weigmann A, Wingen L, Tauscher S, Hinrichsen T, Hertz S, predict clinical phenotype and regional gene expression,
Flemming P, Flik J, Wiese B, Kreipe H, Lichter P, Genes Chromosomes Cancer, 46 (2007) 936.
Schlegelberger B & Wilkens L, Assessment of differentiation 84 Korshunov A, Sycheva R & Golanov A, Genetically distinct
and progression of hepatic tumors using array-based and clinically relevant subtypes of glioblastoma defined by
comparative genomic hybridization, Clin Gastroenterol array-based comparative genomic hybridization (array-
Hepatol, 4 (2006) 1283. CGH), Acta Neuropathol, 111 (2006) 465.
71 Park SJ, Jeong SY & Kim HJ, Y chromosome loss and other 85 Korshunov A, Sycheva R, Golanov A & Pronin I, Gains at
genomic alterations in hepatocellular carcinoma cell lines the 1p36 chromosomal region are associated with
analyzed by CGH and CGH array, Cancer Genet Cytogenet, symptomatic leptomeningeal dissemination of supratentorial
166 (2006) 56. glioblastomas, Am J Clin Pathol, 127 (2007) 585.
72 Harada T, Chelala C, Bhakta V, Chaplin T, Caulee K, Baril 86 Ruano Y, Mollejo M, Ribalta T, Fiaño C, Camacho FI,
P, Young BD & Lemoine NR, Genome-wide DNA copy Gómez E, de Lope AR, Hernández-Moneo JL, Martínez P &
number analysis in pancreatic cancer using high-density Meléndez B, Identification of novel candidate target genes in
single nucleotide polymorphism arrays, Oncogene 27 amplicons of Glioblastoma multiforme tumors detected by
(2008) 1951 expression and CGH microarray profiling, Mol Cancer, 5
73 Harada T, Baril P, Gangeswaran R, Kelly G, Chelala C, (2006) 39.
Bhakta V, Caulee K, Mahon PC & Lemoine NR, 87 Rossi MR, Conroy J, McQuaid D, Nowak NJ, Rutka JT &
Identification of genetic alterations in pancreatic cancer by Cowell JK, Array CGH analysis of pediatric medulloblastomas,
the combined use of tissue microdissection and array-based Genes Chromosomes Cancer, 45 (2006) 290.
comparative genomic hybridisation, Br J Cancer, 96 88 Pfister S, Remke M, Toedt G, Werft W, Benner A,
(2007) 373. Mendrzyk F, Wittmann A, Devens F, von Hoff K, Rutkowski
74 Yamamoto Y, Chochi Y, Matsuyama H, Eguchi S, Kawauchi S, Kulozik A, Radlwimmer B, Scheurlen W, Lichter P &
S, Furuya T, Oga A, Kang JJ, Naito K & Sasaki K, Gain of Korshunov A, Supratentorial primitive neuroectodermal
5p15.33 is associated with progression of bladder cancer, tumors of the central nervous system frequently harbor
Oncology, 72 (2007) 132. deletions of the CDKN2A locus and other genomic
75 Vauhkonen H, Böhling T, Eissa S, Shoman S & Knuutila S, aberrations distinct from medulloblastomas, Genes
Can bladder adenocarcinomas be distinguished from Chromosomes Cancer, 46 (2007) 839.
790 INDIAN J EXP BIOL, OCTOBER 2009

89 Rodrigues R, Roque L, Espadinha C, Pinto A, Domingues R, 101 Shaffer LG & Bejjani BA, Medical applications of array
Dinis J, Catarino A, Pereira T & Leite V, Comparative CGH and the transformation of clinical cytogenetics,
genomic hybridization, BRAF, RAS, RET, and oligo-array Cytogenet Genome Res, 115 (2006) 303.
analysis in aneuploid papillary thyroid carcinomas, Oncol 102 Veltman JA, Genomic microarrays in clinical diagnosis,
Rep, 18 (2007) 917. Curr Opin Pediatr, 18 (2006) 598.
90 Finn S, Smyth P, O'Regan E, Cahill S, Toner M, Timon C, 103 Shaffer LG, Bejjani BA, Torchia B, Kirkpatrick S,
Flavin R, O'Leary J & Sheils O, Low-level genomic Coppinger J & Ballif BC, The identification of micro-
instability is a feature of papillary thyroid carcinoma: an deletion syndromes and other chromosome abnormalities:
array comparative genomic hybridization study of laser cytogenetic methods of the past, new technologies for the
capture microdissected papillary thyroid carcinoma tumors future, Am J Med Genet C Semin Med Genet, 145C(4)
and clonal cell lines, Arch Pathol Lab Med, 131 (2007) 65. (2007) 335.
91 Lee GY, Yang WI, Jeung HC, Kim SC, Seo MY, Park CH, 104 Doco-Fenzy M, Landais E, Andrieux J, Schneider A,
Chung HC & Rha SY, Genome-wide genetic aberrations of Delemer B, Sulmont V, Melin JP, Ploton D, Thevenard J,
thymoma using cDNA microarray based comparative Monboisse JC, Belouadah M, Lefebvre F, Durlach A,
genomic hybridization, BMC Genomics, 8 (2007) 305. Goossens M, Albuisson J, Motte J & Gaillard D, Deletion
92 Kallioniemi A, CGH micro-arrays and cancer, Curr Opin 2q36.2q36.3 with multiple renal cysts and severe mental
Biotechnol, 19 (2008) 6. retardation, Eur J Med Genet, 51 (2008) 598.
93 Sheth FJ, Andrieux J & Sheth JJ, Marker chromosome in a 105 Andrieux J, Lepretre F, Cuisset JM, Goldenberg A, Delobel
child with microcephaly and mental retardation characterize B, Manouvrier-Hanu S & Holder-Espinasse M, Deletion
by array-CGH as trisomy 18p. Ind Pediatr (2009) [In Press] 18q21.2q21.32 involving TCF4 in a boy diagnosed by CGH-
94 Andrieux J, Richebourg S, Duban-Bedu B, Petit F, Leprêtre array, Eur J Med Genet, 51 (2008) 172-7.
F, Sukno S, Dehouck MB & Delobel B, Characterization by 106 Andrieux J, Cuvellier JC, Duban-Bedu B, Joriot-Chekaf S,
array-CGH of an interstitial de novo tandem 6p21.2p22.1 Dieux-Coeslier A, Manouvrier-Hanu S, Delobel B & Vallee
duplication in a boy with epilepsy and developmental delay, L, A 6.9 Mb 1qter deletion/4.4 Mb 18pter duplication in a
Eur J Med Genet, 51 (2008) 373. boy with extreme microcephaly with simplified gyral pattern,
95 Doco-Fenzy M, Holder-Espinasse M, Bieth E, Magdelaine vermis hypoplasia and corpus callosum agenesis, Eur J Med
C, Vincent MC, Khoury M, Andrieux J, Zhang F, Lupski JR, Genet, 51 (2008) 87-91
Klink R, Schneider A, Goze-Martineau O, Cuisset JM, 107 Shaw-Smith C, Redon R, Rickman L, Rio M, Willatt L,
Vallee L, Manouvrier-Hanu S, Gaillard D & de Martinville Fiegler H, Firth H, Sanlaville D, Winter R, Colleaux L,
B, The clinical spectrum associated with a chromosome 17 Bobrow M & Carter N P, Micro-array based comparative
short arm proximal duplication (dup 17p11.2) in three genomic hybridization (array-CGH) detects submicroscopic
patients, Am J Med Genet, 146 (2008) 917. chromosomal deletions and duplications in patients with
96 Maas NM, Van Buggenhout G, Hannes F, Thienpont B, learning disability/mental retardation and dysmorphic
Sanlaville D, Kok K, Midro A, Andrieux J, Anderlid BM, features, J Med Genet, 41 (2004) 241.
Schoumans J, Hordijk R, Devriendt K, Fryns JP & 108 Shaffer LG & Bejjani BA, Medical applications of array
Vermeesch JR, Genotype-phenotype correlation in 21 CGH and the transformation of clinical cytogenetics,
patients with Wolf-Hirschhorn syndrome using high Cytogenet Genome Res, 115 (2006) 303.
resolution array comparative genome hybridisation (CGH), J 109 Shaffer LG, Bejjani BA, Torchia B, Kirkpatrick S,
Med Genet, 45 (2008) 71. Coppinger J & Ballif BC, The identification of microdeletion
97 Leal T, Andrieux J, Duban-Bedu B, Bouquillon S, Brevière syndromes and other chromosome abnormalities: cytogenetic
GM & Delobel B, Array-CGH detection of a de novo 0.8Mb methods of the past, new technologies for the future, Am J
deletion in 19q13.32 associated with mental retardation, Med Genet C Semin Med Genet, 145 ( 2007) 335.
cardiac malformation, cleft lip and palate, hearing loss and 110 Béri-Dexheimer M, Bonnet C, Chambon P, Brochet K,
multiple dysmorphic features, Eur J Med Genet, 52 (2009) 62 Grégoire MJ & Jonveaux P, Microarray-based comparative
98 Shaw-Smith C, Redon R, Rickman L, Rio M, Willatt L, genomic hybridization in the study of constitutional
Fiegler H, Firth H, Sanlaville D, Winter R, Colleaux L, chromosomal abnormalities, Pathol Biol, 55(1) (2007)13.
Bobrow M & Carter N P, Micro-array based comparative 111 Vissers LE, de Vries BB, Osoegawa K, Janssen IM, Feuth T,
genomic hybridization (array-CGH) detects submicroscopic Choy CO, Straatman H, van der Vliet W, Huys EH, van Rijk
chromosomal deletions and duplications in patients with A, Smeets D, van Ravenswaaij-Arts CM, Knoers N , van der
learning disability/mental retardation and dysmorphic Burgt I, de Jong PJ, Brunner HG, van Kessel AG,
features, J Med Genet, 41 (2004) 241. Schoenmakers EF & Veltman JA, Array-based comparative
99 Lockwood W W, Chari R, Chi B & Lam W L, Recent genomic hybridization for the genomewide detection of
advances in array comparative genomic hybridization submicroscopic chromosomal abnormalities, Am J Hum
technologies and their applications in human genetics, Eur J Genet, 73 (2003) 1261.
Hum Genet, 14 (2006)139. 112 Krepischi-Santos AC, Vianna-Morgante AM, Jehee FS,
100 de Vries B B, Pfundt R, Leisink M, Koolen D A, Vissers L Passos-Bueno MR, Knijnenburg J, Szuhai K, Sloos W,
E, Janssen I M, Reijmersdal S, Nillesen W M, Huys E H, Mazzeu JF, Kok F, Cheroki C, Otto PA, Mingroni-Netto RC,
Leeuw N, Smeets D, Sistermans E A, Feuth T, van Varela M, Koiffmann C, Kim CA, Bertola DR, Pearson PL
Ravenswaaij-Arts C M, van Kessel A G, Schoenmakers E F, & Rosenberg C, Whole-genome array-CGH screening in
Brunner H G & Veltman J A, Diagnostic genome profiling in undiagnosed syndromic patients: old syndromes revisited and
mental retardation, Am J Hum Genet, 77 (2005) 606. new alterations, Cytogenet Genome Res, 115 (2006) 254.
ANDRIEUX & SHETH : CGH-ARRAY STUDY & ITS UTILITIES 791

113 Rosenberg C, Knijnenburg J, Bakker E, Vianna-Morgante and review of published reports, J Med Genet, 43 (2006)
AM, Sloos W, Otto PA, Kriek M, Hansson K, Krepischi- 625.
Santos AC, Fiegler H, Carter NP, Bijlsma EK, van 115 Stankiewicz P & Beaudet AL, Use of array CGH in the
Haeringen A, Szuhai K & Tanke HJ, Array-CGH evaluation of dysmorphology, malformations, developmental
detection of micro rearrangements in mentally retarded delay and idiopathic mental retardation, Curr Opin Genet
individuals: clinical significance of imbalances present Dev, 17 (2007) 182.
both in affected children and normal parent, J Med Genet, 116 de Ravel TJ, Devriendt K, Fryns JP & Vermeesch JR,
43 (2006) 180. What’s new in karyotyping? The move towards array
114 Menten B, Maas N, Thienpont B, Buysse K, Vandesompele comparative genomic hybridization (CGH), Eur J Pediatr,
J, Melotte C, de Ravel T, Van Vooren S, Balikova I, Backx 116 (2007) 637.
L, Janssens S, De Paepe A, De Moor B, Moreau Y, Marynen 117 Sheth FJ, Ewers E, Kosyakova N, Weise A, Sheth J, Patil S,
P, Fryns JP, Mortier G, Devriendt K, Speleman F & Ziegler M, Liehr T, A neocentric isochromosome Yp present
Vermeesch J R, Emerging patterns of cryptic chromosomal as additional small supernumerary marker chromosome –
imbalance in patients with idiopathic mental retardation and evidence against U-type exchange mechanism? Cytogenetic
multiple congenital anomalies: a new series of 140 patients Genome Res, 125 (2) (2009) 115