1. Oncogenes and tumour suppressor genes

2. Tumour suppressor genes
oncogenes
Tumour suppressor genes

3. Oncogenes
Genes known as proto-oncogenes code for proteins that stimulate cell division
mutated forms, called oncogenes, cause stimulatory proteins to be overactive, with the result that cells proliferate excessively
gain of function mutations

4. Oncogenes gain of function mutations

5. Some acronyms! Myc Sis Erb Src Ras Yes Abl Fos jun Myelocytomatosis
Simian sarcoma
Erythroblastoma
Rous sarcoma virus
Rat sarcoma
2 viruses Y73 & ESH sarcoma, isolated from a chicken owned by Mr. Esh
Abelson murine leukaemia virus
Finkel biskis jinkins reilly mouse sarcoma
junana

6. Activation of proto-oncogenes
Viral insertion
Chromosomal rearrangements
Altered regulation
Fusion genes
Gene amplification
Point mutations
Loss of degradation signals

7. Viral insertion

8. Chromosomal rearrangements – altered regulation
Burkitts lymphoma
All patients show t(8:14)
translocation of the immunoglobulin gene on chromosome 14 to the c-myc oncogene locus on chromosome 8
c-myc is under regulatory control of IgH resulting in overexpression of the oncogene

9. Chromosomal rearrangements - fusion gene
Chronic Myelogenous Leukaemia
Translocation t(9:22)
Abl-bcr fusion gene encodes a constitutively active protein tyrosine kinase, which affects cell cycle, adhesion and apoptosis

10. point mutations
Point mutations in ras, implicated in bladder carcinoma
e.g. GGC to GTC (G12V)

11. Gene amplification
Metaplastic breast carcinomas (MBCs) account for less than 1% of all invasive mammary carcinomas.
Approximately 70–80% of metaplastic breast carcinomas overexpress the epidermal growth factor receptor (EGFR).
Human epidermal growth factor receptor (HER2)
EGFR gene amplification in MBC (>5 signals per nucleus). Note the bizarre neoplastic cell with more than
10 copies of EGFR.

12. Loss of degradation signals
Epstein–Barr virus (EBV) is a human herpesvirus associated with lymphoid and epithelial malignancies.
Three viral proteins, EBNA1, LMP-1 and -2A, constitutively activate c-myc oncogene by decreasing ubiquitin-dependent proteolysis of this protein and upregulate compensatory pathways in Burkitt’s lymphomas.
Fig. 1. Latent EBV proteins interferes with the ubiquitin/proteasome system. Schematic representation of different manipulations of the ubiquitin/proteasome system by the EBV latent proteins LMP2A, EBNA1 and LMP1. In different colours are depicted viral proteins (red), cellular proteins (green) and components of the ubiquitin/proteasome system (blue). U, ubiquitin; E3, ubiquitin ligase.
Seminars in Cancer Biology Volume 13, Issue 1 , February 2003, Pages 69-76

13. Growth factor signalling and oncogenes
Cell Cycle Control is through the effects of growth factors which interact with membrane-bound glycoprotein receptors that transduce the message via a series of intracellular signals that promote or inhibit the expression of specific genes.

23. Oncogenes and the cell cycle

26. Further examples of oncogenes

27. References