Familial adenomatous polyposis-associated and sporadic pyloric gland adenomas of the upper gastrointestinal tract share common genetic features
Familial adenomatous polyposis-associated and sporadic pyloric gland adenomas of the upper gastrointestinal tract share common genetic features
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DOI：
10.1111/his.12705
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发表时间：
2015-11-01
期刊：
影响因子：
6.4
通讯作者：
Sekine, Shigeki
中科院分区：
文献类型：
--
作者：
Hashimoto, Taiki;Ogawa, Reiko;Sekine, Shigeki
家族性腺瘤性息肉病（FAP）是一种由APC基因突变引起的遗传性癌症易感综合征.最近的一项研究表明，在FAP患者中，除了胃底腺息肉（FGP）和胃小凹型腺瘤（FA）外，胃幽门腺腺瘤（PGA）也会富集。在本研究中，我们分析了这些FAP相关的胃病变的遗传学改变。方法和结果GNAS和KRAS，这是经常突变的散发性PGA，以及APC的突变状态，检查在PGA，FA和FGP在FAP患者使用桑格测序。我们的分析在6个PGA中的5个（83%）中发现了GNAS突变，但在3个FA或40个FGP中没有发现突变。在4例PGA（67%）、1例FA（33%）和1例FGP（3%）中发现了KRAS突变。体细胞截短型APC突变在所有PGA（100%）、2个FA（67%）和14个FGP（47%）中发现。我们还分析了散发性前列腺增生症的胃和十二指肠，并确定截断APC突变11 25病变（44%）。ConclusionsFAP相关和散发性前列腺增生症不仅表现出相似的形态，但也有共同的遗传畸变，包括突变的GNAS，KRAS和APC。
AimsFamilial adenomatous polyposis (FAP) is a hereditary cancer predisposition syndrome caused by a germline APC mutation. A recent study showed the enrichment of pyloric gland adenomas (PGAs) of the stomach, in addition to fundic gland polyps (FGPs) and foveolar-type adenomas (FAs), in patients with FAP. In the present study, we analysed the genetic alterations in these FAP-associated gastric lesions.Methods and resultsMutational statuses of GNAS and KRAS, which are frequently mutated in sporadic PGAs, as well as those of APC, were examined in PGAs, FAs and FGPs in patients with FAP using Sanger sequencing. Our analysis identified GNAS mutations in five of six PGAs (83%), but in none of the three FAs or the 40 FGPs examined. KRAS mutations were identified in four PGAs (67%), one FA (33%) and one FGP (3%). Somatic truncating APC mutations were found in all PGAs (100%), two FAs (67%) and 14 FGPs (47%). We additionally analysed sporadic PGAs of the stomach and duodenum and identified truncating APC mutations in 11 of 25 lesions (44%).ConclusionsFAP-associated and sporadic PGAs not only show similar morphologies, but also share common genetic aberrations, including mutations of GNAS, KRAS and APC.