Mutational profiles of different macroscopic subtypes of colorectal adenoma reveal distinct pathogenetic roles for KRAS, BRAF and PIK3CA

BMC Gastroenterology

Research Article

Li-Chun Chang¹  Ming-Shiang Wu²  Han-Mo Chiu²  Yi-Chia Lee²  Chien-Chuan Chen²  Jaw-Town Lin²  Chia-Tung Shun³  Jin-Tung Liang⁴ 

[1] Department of Internal Medicine, National Taiwan University Hospital, Bei-Hu branch, Taipei, Taiwan;Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan;Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan;Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan;Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan;

关键词: Gene mutation;    Non-polypoid colorectal neoplasm;    EGFR;   

DOI  :  10.1186/s12876-014-0221-y

 received in 2014-09-11, accepted in 2014-12-12,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundInvestigations of genetic alterations and correlations with histology or morphology could provide further insights into colorectal carcinogenesis. Nevertheless, such genetic changes were less investigated in adenoma stage and a comprehensive survey of oncogenic mutations in EGFR signaling pathway according to different morphologic subtypes has not been performed.MethodsA total of 94 neoplasms, including 34 polypoid adenoma, 16 lateral spreading tumors-granular (LST-G), 20 non-granular LST (LST-NG), and 24 depressed tumors, were subjected for mutational analysis of KRAS (exon 2), BRAF (exon 11 and 15), PIK3CA (exon 9 and 20), AKT (exon 4), EGFR (exon 18–24) and HER2 (exon18-24).ResultsKRAS mutation was noted more frequently in LST (13/36, 36.1%) than polypoid neoplasms (5/34, 14.7%, p = 0.041). When comparing with LST-NG, LST-G had a significantly higher frequency of KRAS mutation. (9/16, 56.3% vs. 4/20, 20.0%, p = 0.024). BRAF mutation (V600E) was found in 2 of 36 (5.6%)LSTs and 1 of 34 (2.9%) polypoid lesions. The two LST lesions with BRAF mutation were pathologically proven to be serrated adenoma. PIK3CA mutation (exon 9 E545K) was identified only in LST (5/36, 13.9%). Mutations in KRAS, BRAF or PIK3CA occurred in a mutually exclusive manner. All mutations were absent in the specimens obtained from depressed type neoplasms.ConclusionsThree different macroscopic subtypes of colorectal neoplasms display distinct carcinogenetic pathways in EGFR networking. Further molecular studies of CRCs should take macroscopic subtypes into consideration and highlight the importance of consensus and communication between endoscopic and pathologic diagnosis.

【 授权许可】

Unknown   
© Chang et al.; licensee BioMed Central. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.