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New germline p53 mutation turns up multiple colon tumours

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Japanese researchers have suggested that searches for rogue genes in multiple colon cancer should be broadened to include the p53 mutation. This follows their discovery of a new p53 germline mutation in a patient with multiple primary colon cancers.

The case was of a 73 year old man with one advanced colon carcinoma and five polyps in an area including the caecum and ascending colon. Histological analysis confirmed an advanced carcinoma, two early carcinomas, and three adenomas.

The advanced carcinoma yielded a novel germline p53 mutation of GCC (Ala)→GTC (Val) at codon 189, plus a somatic mutation at codon 245, somatic APC mutations, and a somatic K-ras-2 mutation on genetic analysis. The early carcinomas and adenomas yielded the germline p53 mutation and somatic APC mutations resulting in stop sequences. One early carcinoma had a somatic K-ras-2 mutation.

The case came from a series of 15 patients without germline mutations in the APC gene or DNA mismatch repair genes who had multiple primary colorectal cancers and colorectal polyps without microsatellite instability. Tissue samples from the tumours and adjacent healthy tissue were taken from resected colon for histological and genetic analysis.

The researchers looked for germline p53 mutations because these occur with tumours in multiple organs in Li-Fraumeni syndrome, though it was not known if they might occur with multiple colon cancers. Whether this new germline mutation proves to be pathogenic or a rare polymorphism remains to be determined.