A 28-year-old man from rural India presents with a rapidly enlarging abdominal mass and B symptoms. Biopsy shows medium-sized blastic cells with a "starry sky" pattern, CD20+, CD10+, BCL2-negative, and Ki-67 ≥95%. FISH analysis reveals the translocation marked **A** in the diagram — t(2;8)(p12;q24) placing MYC under control of the kappa immunoglobulin light chain enhancer. Which of the following best describes the biological consequence of this translocation?

Question

Accepted Answer

D. Constitutive MYC activation driving explosive proliferation with the highest Ki-67 in oncology, biologically and clinically identical to the classic t(8;14) translocation. ## Why option 1 is correct

The t(2;8)(p12;q24) translocation places MYC (8q24) under the control of the immunoglobulin kappa light chain enhancer (2p12), resulting in constitutive MYC activation. This is one of three translocations defining Burkitt lymphoma (~15% of cases), and is biologically and clinically identical to the classic t(8;14) translocation. MYC is a master transcription factor that drives ribosomal biogenesis, cell-cycle entry (via CCND2, CDK4), glycolysis, and glutaminolysis. This explosive proliferation is reflected in the pathognomonic Ki-67 ≥95% — the highest in all of oncology — with a doubling time of 24–48 hours. The diagnosis of Burkitt lymphoma is defined by MYC translocation with an immunoglobulin partner, not by loss of BCL2 (which is BCL2-negative in BL) or TP53 fusion.

## Why each distractor is wrong

- **Option 2**: BCL2 is characteristically NEGATIVE in Burkitt lymphoma, not lost. BCL2 overexpression is a hallmark of follicular lymphoma (t(14;18)) and diffuse large B-cell lymphoma, not BL. The t(2;8) translocation does not alter BCL2 expression.
- **Option 3**: TP53 is not translocated in t(2;8). While concurrent TP53 or CDKN2A loss may accelerate disease, the primary pathogenic event is MYC translocation under an immunoglobulin enhancer, not TP53 rearrangement.
- **Option 4**: MYC is not fused to the kappa light chain protein; rather, the MYC gene is placed under the transcriptional control of the kappa light chain enhancer. This results in overexpression of full-length MYC protein, not a chimeric fusion protein with altered DNA-binding capacity.

**High-Yield:** t(2;8) MYC-IGK is a variant translocation in Burkitt lymphoma (~15%) that is biologically identical to t(8;14) — both result in constitutive MYC activation and Ki-67 ≥95%.

[cite: WHO 2022 Lymphoid Classification; Robbins 10e]

Answer

A. Loss of BCL2 expression leading to apoptosis resistance and prolonged cell survival

Answer

B. Fusion of MYC with the kappa light chain gene, creating a chimeric protein with altered DNA-binding capacity

Answer

C. Translocation of TP53 to chromosome 2, resulting in loss of p53-mediated cell cycle checkpoint control

Explanation

Why option 1 is correct

Why each distractor is wrong

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