Genetic changes and histopathological types in colorectal tumors from patients with familial adenomatous polyposis.
Genetic changes and histopathological types in colorectal tumors from patients with familial adenomatous polyposis.
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家族性腺瘤性息肉病患者结直肠肿瘤的遗传变化和组织病理学类型。
作者：
M. Miyaki;M. Seki;Mieko Okamoto;Akiyoshi Yamanaka;Y. Maeda;Kiyoko Tanaka;Rei Kikuchi;Takeo Iwama;Tatsuro Ikeuchi;Akira Tonomura;Yusuke Nakamura;Ray White;Yoshio Miki;Joji Utsunomiya;Morio Koike
对40例不同组织病理类型的家族性腺瘤性息肉病患者的111例大肠息肉和26例大肠浸润癌进行了杂合性缺失（洛）和K-ras基因突变分析。在中度腺瘤中LOH小于2%，在重度腺瘤中LOH位于染色体5 q（20%），在粘膜内癌中LOH位于染色体5 q（26%）和17 p（38%），在浸润性癌中LOH位于染色体5 q（52%）、17 p（56%）、18（46%）和22 q（33%）。5号染色体上的洛在腺瘤和癌中均发生在APC基因附近，3例APC基因正常等位基因丢失。K-ras基因突变在中、重度腺瘤中的发生率分别为11%和36%。这些结果提示家族性腺瘤性息肉病患者发生结肠肿瘤的机制如下：（a）APC基因的杂合突变/野生型条件导致轻度或中度腺瘤的形成：（B）APC基因中正常等位基因的缺失导致中度腺瘤向重度腺瘤的转变;（c）染色体17 p上的洛缺失与腺瘤向黏膜内癌的转化有关，（d）其它染色体上的洛缺失，如18和22 q，与黏膜内癌向浸润癌的转化有关;（e）K-ras基因突变也可能影响中重度腺瘤的发展。
Loss of heterozygosity (LOH) and K-ras mutation were analyzed in 111 colorectal polyps and 26 invasive carcinomas from 40 patients with familial adenomatous polyposis of distinct histopathological types. LOH, being less than 2% in moderate adenomas, was detected on chromosome 5q (20%) in severe adenomas, on 5q (26%) and 17p (38%) in intramucosal carcinomas, and on 5q (52%), 17p (56%), 18 (46%), and 22q (33%) in invasive carcinomas. LOH on chromosome 5q occurred most frequently in the region close to the APC gene both in adenomas and carcinomas, and a loss of the normal allele of the APC gene was demonstrated in 3 cases. K-ras mutation markedly increased in the step of development from moderate (11%) to severe (36%) adenomas. These results suggest the following mechanisms for the development of colon tumors in patients with familial adenomatous polyposis: (a) the heterozygous mutant/wild-type condition at the APC gene causes formation of mild or moderate adenoma; (b) the loss of the normal allele in the APC gene leads to a change from moderate to severe adenoma; (c) LOH on chromosome 17p contributes to the conversion of adenoma to intramucosal carcinoma; (d) LOH on other chromosomes, such as 18 and 22q, are involved in the progression of intramucosal carcinoma to invasive carcinoma; and (e) K-ras mutation may also affect the development of moderate to severe adenoma.
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一个匿名 DNA 片段 (II227) 映射到人类 5 号染色体的长臂，并鉴定出 BstXI 多态性 (D5S26)。
影响因子：
14.9
作者：
Stewart,GD;Bruns,GA;Wasmuth,JJ;Kurnit,DM
通讯作者：
Kurnit,DM
影响因子：
56.9
作者：
LEPPERT, M;DOBBS, M;WHITE, R
通讯作者：
WHITE, R
影响因子：
56.9
作者：
FEARON, ER;HAMILTON, SR;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
56.9
作者：
BAKER, SJ;FEARON, ER;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
56.9
作者：
FEARON, ER;CHO, KR;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B