Akiyama Y, Iwanaga R, Saitoh K, Shiba K, Ushio K, Ikeda E, Iwama T, Nomizu T, Yuasa Y
Department of Hygiene and Oncology, School of Medicine, Tokyo Medical and Dental University, Japan.
Gastroenterology. 1997 Jan;112(1):33-9. doi: 10.1016/s0016-5085(97)70216-6.
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.
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.
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.
These data indicate a strong association between TGF-beta RII gene alterations and adenoma-carcinoma progression in HNPCC.
DNA错配修复基因的种系突变是遗传性非息肉病性结直肠癌（HNPCC）家族癌症易感性的原因。已发现转化生长因子βII型受体（TGF-βRII）在HNPCC中发生体细胞改变。本研究的目的是进一步阐明TGF-βRII改变在HNPCC肿瘤发生中的作用，特别是在腺瘤中。
通过聚合酶链反应-单链构象多态性对10例HNPCC患者的14个腺瘤标本和13个癌标本进行TGF-βRII基因短重复序列突变筛查。还对HNPCC肿瘤中的错配修复基因、复制错误和c-K-ras 2进行了分析。
在8个（57%）腺瘤标本和11个（85%）癌标本中发现了TGF-βRII基因在短聚腺苷酸重复序列处的改变。它们在腺瘤的早期阶段被发现。两个腺瘤标本显示错配修复基因的双打击失活。在13个（93%）腺瘤标本中可检测到复制错误。腺瘤标本中c-K-ras 2密码子12的突变频率为50%。
这些数据表明TGF-βRII基因改变与HNPCC中的腺瘤-癌进展密切相关。
