Inherited susceptibility to colorectal adenomas and carcinomas: Evidence for a new predisposition gene on 15q14-q22
Inherited susceptibility to colorectal adenomas and carcinomas: Evidence for a new predisposition gene on 15q14-q22
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DOI：
10.1016/s0016-5085(99)70061-2
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发表时间：
1999-04-01
期刊：
影响因子：
29.4
通讯作者：
Stratton, MR
中科院分区：
文献类型：
--
作者：
Tomlinson, I;Rahman, N;Stratton, MR
背景和目标：本研究的目的是评估已知的结直肠腺瘤和癌易感基因的作用，并找到一个新的易感基因在德系犹太人家庭（SM 1311）与显性遗传倾向结直肠腺瘤和癌。方法：收集临床病理和家族史资料。遗传连锁和突变分析被用来调查该家族疾病的遗传基础。结果如下：受影响的成员SM 1311发展多个管状，绒毛状，管状绒毛状，和/或锯齿状结直肠腺瘤整个大肠，和一些发展结肠癌。在SM 1311中没有与疾病明确相关的结肠外特征。我们已经表明，该家族的表型并不是由APC突变（包括l1307 K变异）或其他已知的易患结肠癌的基因的遗传变化引起的。利用遗传连锁分析，辅以肿瘤等位基因丢失，我们提供了一个新的大肠癌易感基因，CRAC 1（大肠腺瘤和癌），定位于染色体15 q14-q22的证据。结论：本研究为染色体15 q14-q22上存在一个新的大肠腺瘤和大肠癌易感基因提供了证据。需要进一步的研究来证实这种定位，并评估CRAC 1的贡献。这种疾病。
Background & Aims: The aim of this study was to evaluate the role of known colorectal adenoma and carcinoma susceptibility genes and to locate a novel susceptibility gene in an Ashkenazi family (SM1311) with dominantly inherited predisposition to colorectal adenomas and carcinomas. Methods: Clinicopathologic and family history data were collected. Genetic linkage and mutational analyses were used to investigate the genetic basis of the family's disease. Results: Affected members of SM1311 develop multiple tubular, villous, tubulovillous, and/or serrated colorectal adenomas throughout the large bowel, and some develop colon carcinoma. There are no extracolonic features clearly associated with disease in SM1311. We have shown that the family's phenotype does not result from APC mutations (including the l1307K variant) or from genetic changes in the other known genes that predispose to colon cancer. Using genetic linkage analysis, supplemented by allele loss in tumors, we have provided evidence for a new colorectal cancer susceptibility gene, CRAC1 (colorectal adenoma and carcinoma), mapping to chromosome 15q14-q22. Conclusions: We provide evidence for a novel colorectal adenoma and carcinoma susceptibility gene on chromosome 15q14-q22. Further studies are needed to confirm this localization and to evaluate the contribution of CRAC1. to this disease.