A tumor demonstrates simultaneous loss of heterozygosity (LOH) at 3p, 5q, 17p, and 18q. This pattern of chromosomal instability is most consistent with the development of which carcinoma via the chromosomal instability (CIN) pathway?

• A Microsatellite-unstable colorectal carcinoma
• B Sporadic colorectal carcinoma via CIN pathway ✓
• C Hereditary non-polyposis colorectal cancer (Lynch syndrome)
• D Serrated pathway colorectal carcinoma

Explanation

The CIN pathway in sporadic colorectal carcinoma involves sequential LOH at APC (5q), KRAS mutation, SMAD4/DPC4 (18q) loss, and TP53 (17p) loss — the Vogelstein adenoma-carcinoma sequence. LOH at 3p suggests VHL or FHIT involvement in some tumors. Lynch syndrome carcinomas show microsatellite instability (MSI-H) with intact chromosomal stability. The serrated pathway involves BRAF mutation and CpG island methylator phenotype (CIMP).

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.