Patterns of PIK3CA alterations in familial colorectal and endometrial carcinoma
Patterns of PIK3CA alterations in familial colorectal and endometrial carcinoma
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DOI：
10.1002/ijc.22768
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发表时间：
2007-08-15
影响因子：
6.4
通讯作者：
Peltomaki, Paivi
中科院分区：
文献类型：
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作者：
Ollikainen, Miina;Gylling, Annette;Peltomaki, Paivi
虽然已知磷脂酰肌醇3-激酶(PI3K)/AKT信号通路在多种散发性肿瘤中被激活，但该信号通路在家族性肿瘤中的作用尚不清楚。我们在总共160例家族性结直肠癌(CRC)和子宫内膜癌(EC)中寻找PI3K(PIK3CA)、PTEN和KRAS催化区域的变化，所有这些都可能有助于PI3K/AKT通路的激活，根据DNA错配修复(MMR)基因有无胚系突变进行分层。10/70(14%)和19/90(21%)癌组织发生PIK3CA突变(包括点突变或低水平扩增，两者互斥，1例例外)。在EC中，扩增与MMR基因缺乏胚系突变的亚组(家族性部位特异性子宫内膜癌)显著相关(p=0.015)。无论MMR基因突变状态如何，PTEN表达降低或缺失是子宫内膜癌发生的特征(51/81，63%，EC：24/62，39%，P=0.004)和大肠肿瘤KRAS突变(19/70，27%：9/89，10%，P=0.006)。PIK3CA改变常与PTEN或KRAS改变并存。结合已发表的关于散发性肿瘤的研究，我们的数据拓宽了对PI3K途径基因在人类肿瘤发生中的作用的理解。(C)2007年Wiley-Liss，Inc.
While the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is known to be activated in multiple sporadic cancers, the role of this pathway in familial tumors is mostly unknown. We searched for alterations in the catalytic domain of PI3K (PIK3CA), PTEN and KRAS, all of which may contribute to PI3K/AKT pathway activation, in a total of 160-familial colorectal (CRC) and endometrial carcinomas (EC), stratified by the presence vs. absence of germline mutations in DNA mismatch repair (MMR) genes. PIK3CA alterations (consisting of point mutations or low-level amplification, which were mutually exclusive with 1 exception) occurred in 10/70 (14%) of CRCs and 19/90 (21%) of ECs. Within ECs, amplification was significantly associated with the subgroup lacking germline mutations in MMR genes (familial site-specific endometrial cancer) (p = 0.015). Decreased or lost PTEN expression was characteristic of endometrial tumourigenesis (51/81, 63%, in EC compared with 24/62, 39%, in CRC, p = 0.004) and KRAS mutations of colorectal tumourigenesis (19/70, 27% in CRC vs. 9/89, 10%, in EC, p = 0.006) regardless of the MMR gene mutation status. PIK3CA alterations frequently coexisted with PTEN or KRAS changes. Combined with published studies on sporadic tumors, our data broaden the understanding of the role for PI3K pathway genes in human tumorigenesis. (c) 2007 Wiley-Liss, Inc.