GNAS mutations are present in colorectal traditional serrated adenomas, serrated tubulovillous adenomas and serrated adenocarcinomas with adverse prognostic features

Liu, Cheng, Mckeone, Diane M. , Walker, Neal I. , Bettington, Mark L. , Leggett, Barbara A. and Whitehall, Vicki L. J. (2017) GNAS mutations are present in colorectal traditional serrated adenomas, serrated tubulovillous adenomas and serrated adenocarcinomas with adverse prognostic features. Histopathology, 70 7: 1079-1088. doi:10.1111/his.13180


Author Liu, Cheng
Mckeone, Diane M.
Walker, Neal I.
Bettington, Mark L.
Leggett, Barbara A.
Whitehall, Vicki L. J.
Title GNAS mutations are present in colorectal traditional serrated adenomas, serrated tubulovillous adenomas and serrated adenocarcinomas with adverse prognostic features
Formatted title
GNAS mutations are present in colorectal traditional serrated adenomas, serrated tubulovillous adenomas and serrated adenocarcinomas with adverse prognostic features
Journal name Histopathology   Check publisher's open access policy
ISSN 1365-2559
0309-0167
Publication date 2017-03-22
Sub-type Article (original research)
DOI 10.1111/his.13180
Open Access Status Not yet assessed
Volume 70
Issue 7
Start page 1079
End page 1088
Total pages 10
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Collection year 2018
Language eng
Formatted abstract
Aims: Activating mutations in GNAS are important in the development of a range of neoplasms, including a small proportion of conventional adenomas and colorectal carcinomas (CRCs). However, their contribution to serrated pathway neoplasia is unclear, as mutations have only been examined in small series of sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs), and not in serrated tubulovillous adenomas (sTVAs). The aim of this study was to investigate the frequency and significance of GNAS mutations in colorectal adenomas and CRCs.

Methods and results: Using a large, well-characterized series, we identified GNAS mutations in 9.2% (18 of 196) of TSAs, 7.1% (four of 56) of sTVAs and 2.0% (nine of 459) of CRCs. Mutations were absent in SSAs (none of 43), tubular adenomas (none of 50) and conventional tubulovillous adenomas (none of 50). A BRAF or KRAS mutation was seen in 77.4% of GNAS mutant lesions, suggesting a synergistic effect with the mitogen-activated protein kinase pathway. In CRCs, GNAS mutations were associated with mucinous differentiation and serrated morphological features.

Conclusions: GNAS mutations contribute significantly to the development of a subset of serrated adenomas and CRCs.
Keyword GNAS
Serrated adenocarcinoma
Serrated tubulovillous adenoma
Sessile serrated adenoma
Traditional serrated adenoma
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
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