Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia.
Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia.
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DOI：
10.1038/bjc.2017.148
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发表时间：
2017-06-27
影响因子：
8.8
通讯作者：
Satyamoorthy K
中科院分区：
文献类型：
--
作者：
Chakrabarty S;Varghese VK;Sahu P;Jayaram P;Shivakumar BM;Pai CG;Satyamoorthy K
长期溃疡性结肠炎（UC）导致结直肠癌（CRC）是全球公认的最严重和危及生命的后果之一。与散发性结直肠癌相比，溃疡性结肠炎相关的结直肠癌发生表现出明显的分子改变。对18例长期存在结直肠癌（UC）高风险的UC受试者的组织样本中的409个基因进行靶向测序，以确定体细胞驱动突变，这些突变可能参与非异型增生粘膜向高度异型增生转化期间的分子变化。研究结果还与先前发表的炎症性肠病相关和散发性结直肠癌的全基因组和外显子组测序数据进行了比较。下一代测序分析在UC27受试者的275个基因中发现了1107个突变。除了TP53（17%）和KRAS（22%）突变外，在Ucrose受试者中还观察到APC（33%）、ACVR2A（61%）、ARID1A（44%）、RAF1（39%）和MTOR（61%）的复发突变。此外，在UAE受试者中鉴定了APC、FGFR3、FGFR2和PIK3CA驱动突变。在尿激酶受试者中发现了参与组蛋白修饰和染色质重塑的ARID1A（44%）、SMARCA 4（17%）、MLL2（44%）、MLL3（67%）、SET D2（17%）和TET 2（50%）基因的复发性突变。我们的研究确定了新的致癌驱动突变，这些突变可能参与长期UC受试者中非异型增生细胞向异型增生表型的转变，这些受试者具有进展为结直肠肿瘤的高风险。
Long-standing ulcerative colitis (UC) leading to colorectal cancer (CRC) is one of the most serious and life-threatening consequences acknowledged globally. Ulcerative colitis-associated colorectal carcinogenesis showed distinct molecular alterations when compared with sporadic colorectal carcinoma. 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. 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. 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.
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影响因子：
6.4
作者：
Aust, DE;Haase, M;Tannapfel, A
通讯作者：
Tannapfel, A
DOI：
10.1093/bioinformatics/btt017
发表时间：
2013-03-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Douville C;Carter H;Kim R;Niknafs N;Diekhans M;Stenson PD;Cooper DN;Ryan M;Karchin R
通讯作者：
Karchin R
癌症驱动器MLL2的突变导致转录应力和基因组不稳定性。
影响因子：
10.5
作者：
Kantidakis T;Saponaro M;Mitter R;Horswell S;Kranz A;Boeing S;Aygün O;Kelly GP;Matthews N;Stewart A;Stewart AF;Svejstrup JQ
通讯作者：
Svejstrup JQ
影响因子：
3.2
作者：
Dhir, Mashaal;Montgomery, Elizabeth A.;Glockner, Sabine C.;Schuebel, Kornel E.;Hooker, Craig M.;Herman, James G.;Baylin, Stephen B.;Gearhart, Susan L.;Ahuja, Nita
通讯作者：
Ahuja, Nita
影响因子：
48
作者：
Gonzalez-Perez A;Perez-Llamas C;Deu-Pons J;Tamborero D;Schroeder MP;Jene-Sanz A;Santos A;Lopez-Bigas N
通讯作者：
Lopez-Bigas N