Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms.
Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms.
复制标题
低度阑尾粘液性肿瘤中常见的 GNAS 突变。
DOI：
10.1038/bjc.2013.47
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发表时间：
2013-03-05
影响因子：
8.8
通讯作者：
Kanai, Y.
中科院分区：
文献类型：
--
作者：
Nishikawa, G.;Sekine, S.;Ogawa, R.;Matsubara, A.;Mori, T.;Taniguchi, H.;Kushima, R.;Hiraoka, N.;Tsuta, K.;Tsuda, H.;Kanai, Y.
阑尾粘液性肿瘤是腹膜假性粘液瘤的原因之一，其发生的分子基础仍不清楚。对35例阑尾粘液性肿瘤进行了GNAS和KRAS突变分析。使用结直肠癌细胞系对突变型GNAS进行了功能分析。突变分析发现，32例低度阑尾粘液性肿瘤(LAMN)中有16例存在激活的GNAS突变，但在3例粘液性腺癌(MACs)中均未发现。在30个LAMN和所有MAC中发现KRAS突变。此外，我们还分析了186例阑尾外粘液性肿瘤，发现GNAS突变在胰腺导管内乳头状粘液性肿瘤中非常常见(88%)，但在结肠、卵巢、肺和乳腺的粘液性肿瘤中很少或不存在(0-9%)。KRAS突变的流行率在不同的肿瘤中差异很大。将突变的GNAS导入结直肠癌细胞系后，显著诱导了MUC2和MUC5AC的表达，但在体外和体内均未促进细胞生长。激活GNAS突变是LAMN常见且具有特征性的遗传异常。突变的GNAS可能在LAMN显著的粘蛋白产生中发挥直接作用，这是LAMN的一个标志。
The molecular basis for the development of appendiceal mucinous tumours, which can be a cause of pseudomyxoma peritonei, remains largely unknown. Thirty-five appendiceal mucinous neoplasms were analysed for GNAS and KRAS mutations. A functional analysis of mutant GNAS was performed using a colorectal cancer cell line. A mutational analysis identified activating GNAS mutations in 16 of 32 low-grade appendiceal mucinous neoplasms (LAMNs) but in none of three mucinous adenocarcinomas (MACs). KRAS mutations were found in 30 LAMNs and in all MACs. We additionally analysed a total of 186 extra-appendiceal mucinous tumours and found that GNAS mutations were highly prevalent in intraductal papillary mucinous tumours of the pancreas (88%) but were rare or absent in mucinous tumours of the colorectum, ovary, lung and breast (0–9%). The prevalence of KRAS mutations was quite variable among the tumours. The introduction of the mutant GNAS into a colorectal cancer cell line markedly induced MUC2 and MUC5AC expression, but did not promote cell growth either in vitro or in vivo. Activating GNAS mutations are a frequent and characteristic genetic abnormality of LAMN. Mutant GNAS might play a direct role in the prominent mucin production that is a hallmark of LAMN.
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发表时间：
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影响因子：
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发表时间：
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