Molecular Basis of carcinogenesis

1. MOLECULAR BASIS OF
CARCINOGENESIS
ROLL NO. 71 TO 80

2. What is the molecular Basis
of cancer?
• Mutation in Genes Result in Altered Protiens
- During Cell Division
-External Agents
-Random Events
• Most Cancers results from Mutation Somatic
cells
• Some Cancers are caused by Mutation in
Germ line

3. Tumor & Hallmarks
• MALIGNANT TUMOR MUST ACQUIRE MULTIPLE HALLMARK
OF CANCER, IT FOLLOWS THAT CANCER RESULT FROM
STEPWISE ACCUMULATION OF MULTIPLE MUTATION THAT
ACT IN COMPLEMENTARY WAYS TO PRODUCE TUMOR
• Hallmarks of tumor
• Self sufficiency in growth signal
• Insensitivity to growth inhibitory signal
• Altered cell metabolism
• Evasion of apoptosis
• Immortality
• Sustained angiogenesis
• Invasion and metastasis
• Evasion of immune surveillance

4. Four Classes of Genes are The Principle Target of
cancer causing Mutation
• Growth Promoting Proto-Oncogenes
• Growth Inhibiting tumor supressor genes
• Genes that Regulate programmed Cell death (Apoptosis)
• Genes Responsible For DNA Repair

5. Theories of Cancer Genesis

8. GENES PLAYING ROLE IN CANCER
DEVELOPMENT
• ONCOGENES
• TUMOR SUPRESSOR GENES
• DNA REPAIR GENES

9. ONCOGENES
• Oncogens are mutated form of cellular proto-oncogenes.
• Proto –oncogenes codes for cellular protiens which regulates normal cell
growth and differentiation.
• Proto-oncogenes – ras
• Oncogenes – mutated ras
Five Types of Protiens Encoded by Proto –oncogenes Participate in Control of Cell
growth –
• Class I – Growth Factor
• Class II – Receptors for growth Factors and Harmones
• Class III –Intracellular Transducers
• Class IV –Nuclear Transcription Factors
• Class V –Cell Cycle Control Protiens
Any Alteration in these encoded protiens form the Basis of Carcinogenesis.

10. Cellular Proto-
oncogenes
The Result –
•Overproduction of
growth factors.
•Flooding of Cell with
Replication Signals.
•Uncontrolled stimulations
in the Intermediary
Pathways.
•Cell Growth by Elevated
Level of transcription
Factors.

11. Tumor Supressor Genes
•Normal Function- Inhibit Cell Proliferation
•Absence/Inactivation- Cancer
•Both Gene Copies Must be Defective to cause
Tumor
Eg – Rb genes, p53, BRCA1, BRCA2, WT1 (wilms Tumor) etc.

12. DNA Repair Genes
• These are genes that ensure each strand of genetic information is
accurately copied during cell division of the cell cycle.
• Mutations in DNA repair genes lead to an increase in the frequency of
mutations in other genes, such as proto-oncogenes and tumor suppressor
genes.
• Breast cancer susceptibility genes (BRCA1 and BRCA2) and
• Hereditary non-polyposis colon cancer
susceptibility genes (MSH2, MLH1, PMS1,
PMS2)
have DNA repair functions.
• Their mutation will cause tumorigenesis.

13. Translocation and Bcr-Abl
fusion in CML

14. Thankyou.....