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Transforming growth factor beta type II receptor gene mutations in adenomas from hereditary nonpolyposis colorectal cancer.

Abstract：

BACKGROUND & AIMS:Germline mutations of DNA mismatch repair genes are responsible for cancer susceptibility in hereditary nonpolyposis colorectal cancer (HNPCC) kindreds. Transforming growth factor beta type II receptor (TGF-beta RII) has been found to be somatically altered in HNPCC. The aim of this study was to clarify further the role of TGF-beta RII alterations in HNPCC tumorigenesis, particularly in adenomas. METHODS:Fourteen adenoma specimens and 13 cancer specimens from 10 patients with HNPCC were screened for mutations in the short repeated sequences of the TGF-beta RII gene by polymerase chain reaction-single-strand conformation polymorphism. Mismatch repair genes, replication errors, and c-K-ras 2 were also analyzed in HNPCC tumors. RESULTS:Alterations of the TGF-beta RII gene at the short poly(A) repeat were found in 8 (57%) adenoma specimens and 11 (85%) cancer specimens. They were found at an earlier stage of adenomas. Two adenoma specimens showed two-hit inactivation of mismatch repair genes. Replication errors were detectable in 13 (93%) adenoma specimens. Mutations in c-K-ras 2 codon 12 were detected at a 50% frequency in adenoma specimens. CONCLUSIONS:These data indicate a strong association between TGF-beta RII gene alterations and adenoma-carcinoma progression in HNPCC.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Akiyama Y,Iwanaga R,Saitoh K,Shiba K,Ushio K,Ikeda E,Iwama T,Nomizu T,Yuasa Y

doi

10.1016/s0016-5085(97)70216-6

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

33-9

issue

1

eissn

0016-5085

issn

1528-0012

pii

S0016508597000176

journal_volume

112

pub_type

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