Past exam of the biochemistry and Molecular Biology course of the University of Cambridge / 2025 / Paper 2 / Section C / 14 / h / Solution

The ascending-colon tumors carry the exon-5 frameshift mutation in $3/4$ sampled patients, transverse tumors in $1/2$, and descending and sigmoid tumors in $0/2$ each. Grouping these gives $4/6$ proximal tumors versus $0/4$ distal tumors with the repeat alteration, suggesting proximal enrichment of this molecular subtype. The matched samples show a one-allele alteration in the adjacent tissue of patients 1 and 7, whereas patients 5 and 9 have tumor-associated alterations without a detected alteration in their matched normal sample.

This is a small case series, and all ten patients already have tumors. It cannot determine whether a region has a higher absolute risk of transformation, nor establish defective DNA mismatch repair from one altered repeat alone. Larger location-matched series, population denominators, testing of additional microsatellites and direct assessment of DNA mismatch repair components are needed to support those stronger claims.