Learning Objective
By the end of this section, learners should be able to explain how proto-oncogenes are converted to oncogenes, recognize the mechanism of gain-of-function mutations, and identify key oncogenes along with their associated cancers.
Key Concepts
- Proto-oncogenes are normal genes that regulate cell growth and differentiation.
- A gain-of-function mutation can convert a proto-oncogene into an oncogene, increasing cancer risk.
- Only one allele needs to be mutated for oncogenic activation.
- Oncogenes often encode proteins involved in signal transduction, transcription regulation, or apoptosis inhibition.
Major Oncogenes, Their Products, and Associated Neoplasms
| Gene | Gene Product | Associated Neoplasm |
|---|---|---|
| ALK | Receptor tyrosine kinase | Lung adenocarcinoma |
| EGFR (ERBB1) | Receptor tyrosine kinase | Lung adenocarcinoma |
| HER2 (ERBB2) | Receptor tyrosine kinase | Breast and gastric carcinomas |
| RET | Receptor tyrosine kinase | MEN2A/2B, medullary thyroid carcinoma, pheochromocytoma |
| BCR-ABL | Non-receptor tyrosine kinase | CML, ALL |
| JAK2 | Non-receptor tyrosine kinase | Myeloproliferative neoplasms |
| BRAF | Serine/threonine kinase | Melanoma, non-Hodgkin lymphoma, colorectal carcinoma, papillary thyroid carcinoma, hairy cell leukemia |
| c-KIT (CD117) | Cytokine receptor | Gastrointestinal stromal tumor (GIST), mastocytosis |
| MYCC (c-myc) | Transcription factor | Burkitt lymphoma |
| MYCN (N-myc) | Transcription factor | Neuroblastoma |
| KRAS | RAS GTPase | Pancreatic, colorectal, lung, and endometrial cancers |
| BCL-2 | Anti-apoptotic molecule | Follicular and diffuse large B-cell lymphomas |
Activity
High-Yield Exam Pearls
- Oncogenes require mutation of only one allele (dominant effect).
- Kinases (ALK, EGFR, HER2, RET, BCR-ABL, JAK2, BRAF) are common targets for molecular therapies.
- BCL-2 prevents apoptosis, contributing to lymphoma development.
- MYC family regulates transcription and drives proliferation in hematologic malignancies.
- KRAS mutations activate downstream signaling, commonly in GI and lung cancers.
