Which of the following oncogenes is most commonly activated by chromosomal translocation in human cancers?

Question

Accepted Answer

D. MYC. ## Oncogene Activation by Translocation

**Key Point:** MYC is the proto-oncogene most frequently activated by chromosomal translocation, particularly in hematologic malignancies. The classic example is t(8;14) in Burkitt lymphoma.

### MYC Translocation Patterns

**High-Yield:** MYC activation by translocation occurs in:
- **Burkitt lymphoma:** t(8;14)(q24;q32) — MYC juxtaposed to immunoglobulin heavy chain (IGH) locus
- **Variant translocations:** t(2;8) and t(8;22) — MYC with kappa and lambda light chain loci
- **Other B-cell lymphomas:** t(8;14) in diffuse large B-cell lymphoma (DLBCL)

### Mechanism of MYC Activation by Translocation

1. Translocation places MYC coding sequence adjacent to highly active immunoglobulin or T-cell receptor promoter
2. MYC transcription driven by constitutively active immunoglobulin/TCR enhancer
3. Overexpression of MYC protein (transcription factor)
4. Uncontrolled cell proliferation and apoptosis resistance

### Comparison of Activation Mechanisms

| Oncogene | Primary Mechanism | Example |
| --- | --- | --- |
| MYC | Translocation | t(8;14) in Burkitt lymphoma |
| RAS | Point mutation | Codon 12/13/61 mutations |
| EGFR | Point mutation, amplification | Exon 19 deletions in lung cancer |
| BCR-ABL | Translocation | t(9;22) in CML |
| HER2 | Gene amplification | Breast cancer |

**Clinical Pearl:** MYC translocations are hallmark lesions in Burkitt lymphoma and are used diagnostically via FISH (fluorescence in situ hybridization) and cytogenetics.

**Mnemonic:** **MYC = Make Your Cell proliferate** — transcription factor driving uncontrolled growth when overexpressed via translocation.

### Why MYC is Most Common for Translocation

- MYC is a transcription factor; overexpression alone drives transformation
- Immunoglobulin and TCR loci are naturally active in lymphoid cells
- Translocations are detectable and diagnostically significant
- Occurs early in lymphomagenesis

[cite:Robbins 10e Ch 7]

Answer

A. RAS

Answer

B. EGFR

Answer

C. KRAS

Which of the following oncogenes is most commonly activated by chromosomal translocation in human cancers?

Explanation

Oncogene Activation by Translocation

MYC Translocation Patterns

Mechanism of MYC Activation by Translocation

Comparison of Activation Mechanisms

Why MYC is Most Common for Translocation

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Oncogene	Primary Mechanism	Example
MYC	Translocation	t(8;14) in Burkitt lymphoma
RAS	Point mutation	Codon 12/13/61 mutations
EGFR	Point mutation, amplification	Exon 19 deletions in lung cancer
BCR-ABL	Translocation	t(9;22) in CML
HER2	Gene amplification	Breast cancer