Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia

Chakrabarty, Sanjiban and Varghese, Vinay Koshy and Sahu, Pranoy and Pradyumna, Jayarama and Shivakumar, BM and Pai, Ganesh C and Satyamoorthy, K (2017) Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia. British Journal of Cancer, 117. pp. 136-143. ISSN 0007-0920

[img] PDF
00002868.pdf - Published Version
Restricted to Registered users only

Download (1MB) | Request a copy


Background: Long-standing ulcerative colitis (UC) leading to colorectal cancer (CRC) is one of the most serious and lifethreatening consequences acknowledged globally. Ulcerative colitis-associated colorectal carcinogenesis showed distinct molecular alterations when compared with sporadic colorectal carcinoma. Methods: Targeted sequencing of 409 genes in tissue samples of 18 long-standing UC subjects at high risk of colorectal carcinoma (UCHR) was performed to identify somatic driver mutations, which may be involved in the molecular changes during the transformation of non-dysplastic mucosa to high-grade dysplasia. Findings from the study are also compared with previously published genome wide and exome sequencing data in inflammatory bowel disease-associated and sporadic colorectal carcinoma. Results: Next-generation sequencing analysis identified 1107 mutations in 275 genes in UCHR subjects. In addition to TP53 (17%) and KRAS (22%) mutations, recurrent mutations in APC (33%), ACVR2A (61%), ARID1A (44%), RAF1 (39%) and MTOR (61%) were observed in UCHR subjects. In addition, APC, FGFR3, FGFR2 and PIK3CA driver mutations were identified in UCHR subjects. Recurrent mutations in ARID1A (44%), SMARCA4 (17%), MLL2 (44%), MLL3 (67%), SETD2 (17%) and TET2 (50%) genes involved in histone modification and chromatin remodelling were identified in UCHR subjects. Conclusions: Our study identifies new oncogenic driver mutations which may be involved in the transition of non-dysplastic cells to dysplastic phenotype in the subjects with long-standing UC with high risk of progression into colorectal neoplasia.

Item Type: Article
Uncontrolled Keywords: Ulcerative colitis; targeted sequencing; ion torrent; somatic mutations.
Subjects: Medicine > KMC Manipal > Gastroenterology
Life Sciences > MLSC Manipal
Depositing User: KMC Library
Date Deposited: 10 Jul 2017 03:57
Last Modified: 10 Jul 2017 03:57

Actions (login required)

View Item View Item