Spirio L N, Kutchera W, Winstead M V, Pearson B, Kaplan C, Robertson M, Lawrence E, Burt R W, Tischfield J A, Leppert M F, Prescott S M, White R
Department of Human Genetics, University of Utah, Salt Lake City, 84112, USA.
Cancer Res. 1996 Mar 1;56(5):955-8.
Mutation of Pla2g2a, a secretory phospholipase A(2) gene, dramatically increases the number of intestinal polyps that develop in the multiple intestinal neoplasia (Min) mouse, a murine model for adenomatous polyposis coli in humans. We tested the hypothesis that mutation of the human homologue(s) of this gene might be responsible for the more severe phenotype (hundreds of polyps) seen in a subset of individuals with attenuated adenomatous polyposis coli (AAPC). DNA sequence analysis demonstrated that alterations of PLA2G2A, as well as related genes PLA2G2C and PLA2G5, were evenly distributed between three classes of AAPC subjects: those with small, intermediate, and large numbers of adenomatous colonic polyps. Among 67 additional unrelated AAPC subjects, a stop mutation in PLA2G2C did not correlate with an increased burden of adenomatous polyps. Therefore, mutation of the human homologue(s) of murine Pla2g2a does not appear to be responsible for phenotypic variation among subjects with AAPC.
分泌型磷脂酶A2基因Pla2g2a的突变，会显著增加多发性肠道肿瘤（Min）小鼠肠道息肉的数量，Min小鼠是人类腺瘤性息肉病的一种鼠类模型。我们验证了这样一个假说：该基因的人类同源基因发生突变，可能是导致一部分患轻度腺瘤性息肉病（AAPC）的个体出现更严重表型（数百个息肉）的原因。DNA序列分析表明，PLA2G2A以及相关基因PLA2G2C和PLA2G5的改变，在三类AAPC受试者中分布均匀：分别是患有少量、中等数量和大量结肠腺瘤性息肉的受试者。在另外67名无亲缘关系的AAPC受试者中，PLA2G2C中的一个终止突变与腺瘤性息肉负担增加无关。因此，小鼠Pla2g2a的人类同源基因发生突变，似乎并不是AAPC受试者之间表型差异的原因。
