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Genetic instability and mutation of the TGF-β-receptor-II gene in ampullary carcinomas

✍ Scribed by Yasuo Imai; Naomi Tsurutani; Hideaki Oda; Tohru Inoue; Takatoshi Ishikawa

Publisher
John Wiley and Sons
Year
1998
Tongue
French
Weight
240 KB
Volume
76
Category
Article
ISSN
0020-7136

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✦ Synopsis

Ampullary carcinomas are relatively rare cancers of which very little is known in terms of carcinogenetic mechanisms at the molecular level. Genetic instability caused by mutations of mismatch-repair genes has been demonstrated to be responsible for hereditary non-polyposis colorectal cancers and a sub-set of sporadic colorectal cancers. In some of those tumors showing genetic instability, the transforming-growthfactor-␤(TGF-␤)-receptor-II gene has been found to be mutated in repetitive sequences and considered to be a target of replication error. We studied the role of genetic instability and associated TGF-␤-receptor-II-gene mutations in a series of 18 sporadic cases by analyzing 5 microsatellite loci (D2S123, D3S1029, D5S409, TP53 and BAT26) and by sequencing a poly-A repeat (nucleotides 709-718) in the TGF-␤-receptor-II gene. Microsatellite instability was observed in 4 (22.2%) and gene mutations in 14 (77.8%) cases. These data indicate that the TGF-␤-receptor-II gene might be a preferential target of genetic instability whose alteration might be specifically advantageous and constitute a common step in the development of ampullary carcinomas.

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