Molecular Basis Of

Cancer
Dr Manjiri
 Genetic damage lies
at the heart of
cancer
Damage related to cell-proliferation
• Normal cell proliferation is
controlled by various genes.

• Damage to these genes = Tumour

 Cell Proliferation

A) Proliferation B) Proliferation
activators suppressors

Both factors are products of genes.

Proto-Oncogenes Tumour supressor genes
Disordered cell proliferation

• 1) Overproduction of
proliferation activators

• 2) Reduction of supressors
• 3) DNA repair genes
• 4) Apoptotic genes
Cancer-Gene classes
1) Oncogenes
2) Tumour suppressor genes
3) Apoptosis genes
4) DNA repair genes
 Normal cell

1) DNA damage - Nonlethal

2) Damage Remains Unrepaired

3) Escapes Apoptosis

Cancer cell
 1) Oncogenes
Michel Bishop ,
Harold Varmus got
Nobel Prize in
1989 for the
discovery of
Oncogenes
Proto-oncogenes ( original gene )
Normal gene for proliferation factor

Oncogene (Altered proto-oncogene)

Oncoproteins
 Examples

• 1) Mutations
– ras – Colon adenocarcinoma
• 2) Gene Rearrangements
– t (8;14) – Burkitt Lymphoma
– t (9;22) – Chronic myeloid leukemia
• 3) Gene Amplification
– N-myc - Neuroblastoma
Gene Amplification: Neuroblastoma

Kumar et al. Basic Pathology 6th ed. Fig. 6-20

Types of Oncogenes
 Oncogene- Classes

1) Growth Factors
2) Growth Factor
Receptors
3) Signal Transducers
4) Transcription
Factors
5) Cell cycle Factors
 Oncogene- Classes
• Growth Factors
- PDGF, TGF
• Growth Factor Receptors
– ret, Her2/neu, c-kit
• Signal Transducers
– Ras, BCR-ABL
• Nuclear Transcription Proteins
– myc
• Cyclin and Cyclin-Dependent Kinases-
-- Cyclin D, Cyclin E, CDK 4
2)Tumour Suppressor Genes
Anti-oncogenes
Tumour Supressor Genes
• DELETED OR INACTIVATED

– RB (Retinoblastoma)
– p53 (70% Of Human Cancers)
 Rb Gene

• Located on
chromosome 13
• Deletion of gene or
complete loss of
chromosome 13
• Loss of cell-cycle
brake
 TP53 : p53

• Located on chromosome 17

• Molecular policeman (guardian of

Genome)

• >50% of human cancers show

mutations of this gene

• Homozygous loss is seen in

carcinomas of lung, breast and colon
 Other Tumour Suppressor
Genes
• Growth Inhibitory Factors
– BRCA-1, BRCA-2, APC
• Molecules that Regulate Signal Transduction

– NF-1
• Molecules that Regulate Nuclear
Transcription and Cell Cycle
– Rb
– P53
– PTEN
 Apotosis and Genes
Pro-apoptotic Anti-apoptotic
• BAX • BCL-2
• BAK • BCL-XL
• P53 Over expression of
• PTEN BCL-2 common in
Impaired function in cancer
cancer
 Normal cell

1) DNA damage - Nonlethal

2) Damage Remains unrepaired

3) Escapes Apoptosis

4) Escapes Immunity

5) Good Angiogenesis

Cancer
 Cancer in India
Male Cancer Female Cancer
1. Oral 1. Cervix
2. Esophagus 2. Breast
3. Stomach 3. Oral
4. Lung 4. Esophagus
Leonardo-da-Vinci
Virgin of the Rock