All of the following are examples of oncogenes activated by chromosomal translocation EXCEPT:
A. PML-RARA fusion protein in acute promyelocytic leukemia resulting from t(15;17) translocation
B. MYC oncogene translocated to the immunoglobulin heavy chain locus in Burkitt lymphoma t(8;14)
C. BCR-ABL fusion protein in chronic myeloid leukemia resulting from t(9;22) translocation
D. BRCA1 tumor suppressor gene inactivation through loss of heterozygosity in hereditary breast cancer
Explanation
Oncogene Activation by Chromosomal Translocation
Key Point
Chromosomal translocations can activate oncogenes by creating abnormal fusion proteins or placing proto-oncogenes under control of strong promoters. BRCA1 is a tumor suppressor, not an oncogene, and is inactivated through loss of heterozygosity — not translocation-mediated activation.
Mechanism of Translocation-Mediated Oncogene Activation
Translocations activate oncogenes through two main mechanisms:
1.
Fusion protein formation: Two genes fuse to create a chimeric protein with abnormal function
2.
Promoter juxtaposition: Oncogene placed under control of a strong constitutive promoter (e.g., immunoglobulin, T-cell receptor)
Examples of Translocation-Activated Oncogenes
Table
Translocation
Fusion Protein
Cancer
Mechanism
t(9;22)
BCR-ABL
CML
Fusion protein with constitutive tyrosine kinase activity
t(8;14)
MYC-IGH
Burkitt lymphoma
MYC placed under IGH promoter; constitutive overexpression
t(15;17)
PML-RARA
APL
Fusion protein blocks differentiation; sensitive to ATRA
t(12;21)
ETV6-RUNX1
Pediatric ALL
Fusion transcription factor
t(11;22)
EWS-FLI1
Ewing sarcoma
Fusion transcription factor
High-YieldNEET PG
BCR-ABL, MYC-IGH, and PML-RARA are classic examples of translocation-activated oncogenes tested in NEET PG.
BRCA1: Tumor Suppressor, Not Oncogene
Key Point
BRCA1 is a tumor suppressor gene that encodes a DNA repair protein. It is inactivated in hereditary breast cancer through:
Loss of heterozygosity (LOH)
Point mutations
Epigenetic silencing
BRCA1 is NOT activated by translocation and does NOT function as an oncogene. Its loss removes a brake on cell division, allowing transformation — this is the opposite of oncogene activation.
Clinical Pearl
BRCA1 mutations follow the two-hit hypothesis (Knudson): germline mutation in one allele, somatic loss of the second allele in target tissue. This is characteristic of tumor suppressors, not oncogenes.
Mnemonic
Oncogenes = Gas pedal (activated by translocation, amplification, mutation); Tumor suppressors = Brakes (inactivated by loss, mutation, epigenetic silencing). BRCA1 is a brake.
Robbins 10e Ch 7
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