Frequent lack of GNAS mutations in colorectal adenocarcinoma associated with GNAS‐mutated villous adenoma. Issue 4 (28th January 2014)

• Record Type: Journal Article
• Authors: Sekine, Shigeki; Ogawa, Reiko; Oshiro, Taihei; Kanemitsu, Yukihide; Taniguchi, Hirokazu; Kushima, Ryoji; Kanai, Yae
• Is Part Of: Genes, chromosomes & cancer. Volume 53:Issue 4(2014:Apr.)
• Page Start: 366
• Page End: 372
• Publication Date: 2014-01-28
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22147
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Colorectal villous adenoma is thought to be associated with a high risk of progression to adenocarcinoma. To better characterize the genetic alterations involved in colorectal carcinogenesis related to villous adenoma, we analyzed mutations in <italic>APC</italic>, <italic>BRAF</italic>, <italic>KRAS</italic>, <italic>TP53</italic>, and <italic>GNAS</italic> in 12 colorectal adenocarcinomas associated with villous adenomas. <italic>APC</italic>, <italic>KRAS</italic>, and <italic>BRAF</italic> mutations were identified in five, 11, and one lesion, respectively, and most of these mutations were shared between the villous adenoma and the adenocarcinoma components in the respective lesions, except in one lesion with <italic>APC</italic> mutations and in two lesions with <italic>KRAS</italic> mutations. <italic>TP53</italic> mutations were observed exclusively in four adenocarcinoma components, consistent with their role in the progression from adenoma to adenocarcinoma. Activating <italic>GNAS</italic> mutations were found in nine villous adenomas; however, unexpectedly, these mutations were shared only in three associated adenocarcinomas. Notably, all six adenocarcinomas with discordant <italic>GNAS</italic> mutation statuses were nonmucinous type, whereas all the other adenocarcinomas, including three adenocarcinomas associated with <italic>GNAS</italic> wild‐type villous adenomas, were mucinous type. The current study suggests that <italic>GNAS</italic>‐mutated villous adenomas may not necessarily be direct precursors of associated adenocarcinomas. At the same time, our observations support the role of activating <italic>GNAS</italic> mutations in increased mucin production in colorectal neoplasms. © 2014 Wiley Periodicals, Inc.</p> </abstract>