Page 227 - Textbook of Pathology, 6th Edition

211

CHAPTER 8

Figure 8.20 Mechanisms of activation of protooncogenes to form growth promoting oncogenes. Neoplasia

is increased secretion of PDGF-β e.g. in gliomas and c) Fibroblast growth factor (FGF): Overexpression of HST-1
sarcomas. protoonogene and amplification of INT-2 protoonogene
b) Transforming growth factor-α (TGF-α): Overexpression of causes excess secretion of FGF e.g. in cancer of the bowel
TGF-α gene occurs by stimulation of RAS protooncogene and breast.
and induces cell proliferation by binding to epidermal growth d) Hepatocyte growth factor (HGF): Overexpression by binding
factor (EGF) receptor e.g. in carcinoma and astrocytoma. to its receptor c-MET e.g. follicular carcinoma thyroid.

 TABLE 8.4: Important Oncogenes, their Mechanism of Activation and Associated Human Tumours.
Type Proto-oncogene Mechanism Associated Human Tumours
1. GROWTH FACTORS
i) PDGF-β SIS Overexpression Gliomas, sarcoma
ii) TGF-α RAS Overexpression Carcinomas, sarcomas
iii) FGF HST-1 Overexpression Bowel cancers
INT-2 Amplification Breast cancer
iv) HGF HGF Overexpression Follicular carcinoma thyroid

2. RECEPTORS FOR GROWTH FACTORS
i) EGF receptors ERB B1(HER 1) Overexpression Squamous cell carcinoma lung, glioblastoma
ERB B2 (HER 2/neu) Amplification Ca breast, ovary, stomach, lungs
ii) c-KIT receptor c-KIT Point mutation GIST
(Steel factor)
iii) RET receptor RET Point mutation MEN type 2A and type 2B, medullary ca thyroid

3. CYTOPLASMIC SIGNAL TRANSDUCTION PROTEINS
GTP-bound RAS Point mutation Common in 1/3rd human tumours, Ca lung, colon,
pancreas
Non-receptor tyrosine BCR-ABL Translocation CML, acute leukaemias
kinase

4. NUCLEAR TRANSCRIPTION FACTORS
C-MYC MYC Translocation Burkitt’s lymphoma
N-MYC MYC Amplification Neuroblastoma, small cell Ca lung
L-MYC MYC Amplification Small cell Ca lung
5. CELL CYCLE REGULATORY PROTEINS
Cyclins Cyclin D Translocation Ca breast, liver, mantle cell lymphoma
Cyclin E Overexpression Ca breast
CDKs CDK4 Amplification Glioblastoma, melanoma, sarcomas