Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer.
Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer.
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DOI：
10.1053/j.gastro.2014.11.042
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发表时间：
2015-03
期刊：
影响因子：
29.4
通讯作者：
Gallinger S
中科院分区：
文献类型：
--
作者：
Grant RC;Selander I;Connor AA;Selvarajah S;Borgida A;Briollais L;Petersen GM;Lerner-Ellis J;Holter S;Gallinger S
我们调查了胰腺癌患者中APC、ATM、BRCA 1、BRCA 2、CDKN 2A、MLH 1、MSH 2、MSH 6、PALB 2、PMS 2、PRSS 1、STK 11和TP 53的生殖系突变的患病率。安大略胰腺癌研究从全省范围的电子病理学数据库中招募了知情同意的胰腺癌参与者;从2003年4月至2012年8月招募了708名先证者。为了提高BRCA 2患病率估计的精确度，根据乳腺癌和/或卵巢癌、胰腺癌或两者皆无的家族史，从3个分层中随机选择290名先证者。使用定制的多基因面板通过下一代测序分析生殖系DNA。根据整个队列的样本计算突变患病率估计值。鉴定了11个致病性突变：ATM中3个，BRCA 1中1个，BRCA 2中2个，MLH 1中1个，MSH 2中2个，MSH 6中1个，TP 53中1个。所有13个基因的突变率为3.8%（95%置信区间，2.1%-5.6%）。在先证者或一级亲属中，携带者状态与乳腺癌显著相关（P<0.01），在先证者或一级亲属中与结直肠癌显著相关（P<0.01），但与胰腺癌家族史、诊断年龄或诊断分期无关。在有乳腺癌和结直肠癌个人或家族史的患者中，分别有10.7%（4.4%-17.0%）和11.1%（3.0%-19.1%）携带致病性突变。一小部分但临床上重要的胰腺癌与已知易感基因的突变有关。本研究中发现的突变的异质性证明了在胰腺癌中使用多基因组的价值。
We investigated the prevalence of germline mutations in APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, and TP53 in patients with pancreatic cancer. The Ontario Pancreas Cancer Study enrolls consenting participants with pancreatic cancer from a province-wide electronic pathology database; 708 probands were enrolled from April 2003 through August 2012. To improve precision of BRCA2 prevalence estimates, 290 probands were randomly selected from 3 strata, based on family history of breast and/or ovarian cancer, pancreatic cancer, or neither. Germline DNA was analyzed by next-generation sequencing using a custom multiple-gene panel. Mutation prevalence estimates were calculated from the sample for the entire cohort. Eleven pathogenic mutations were identified: 3 in ATM, 1 in BRCA1, 2 in BRCA2, 1 in MLH1, 2 in MSH2, 1 in MSH6, and 1 in TP53. The prevalence of mutations in all 13 genes was 3.8% (95% confidence interval, 2.1%–5.6%). Carrier status was significantly associated with breast cancer in the proband or first-degree relative (P<.01), and colorectal cancer in the proband or first-degree relative (P<.01), but not family history of pancreatic cancer, age of diagnosis, or stage at diagnosis. Of patients with a personal or family history of breast and colorectal cancer, 10.7% (4.4%–17.0%) and 11.1% (3.0%–19.1%) carried pathogenic mutations, respectively. A small but clinically important proportion of pancreatic cancer is associated with mutations in known predisposition genes. The heterogeneity of mutations identified in this study demonstrates the value of using a multiple-gene panel in pancreatic cancer.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
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影响因子：
5.2
作者：
Harinck, Femme;Kluijt, Irma;Bruno, Marco J.
通讯作者：
Bruno, Marco J.
影响因子：
4.1
作者：
Bacani, J;Zwingerman, R;Gallinger, S
通讯作者：
Gallinger, S
影响因子：
3.6
作者：
Axilbund JE;Argani P;Kamiyama M;Palmisano E;Raben M;Borges M;Brune KA;Goggins M;Hruban RH;Klein AP
通讯作者：
Klein AP
影响因子：
64.8
作者：
Biankin, Andrew V.;Waddell, Nicola;Kassahn, Karin S.;Gingras, Marie-Claude;Muthuswamy, Lakshmi B.;Johns, Amber L.;Miller, David K.;Wilson, Peter J.;Patch, Ann-Marie;Wu, Jianmin;Chang, David K.;Cowley, Mark J.;Gardiner, Brooke B.;Song, Sarah;Harliwong, Ivon;Idrisoglu, Senel;Nourse, Craig;Nourbakhsh, Ehsan;Manning, Suzanne;Wani, Shivangi;Gongora, Milena;Pajic, Marina;Scarlett, Christopher J.;Gill, Anthony J.;Pinho, Andreia V.;Rooman, Ilse;Anderson, Matthew;Holmes, Oliver;Leonard, Conrad;Taylor, Darrin;Wood, Scott;Xu, Qinying;Nones, Katia;Fink, J. Lynn;Christ, Angelika;Bruxner, Tim;Cloonan, Nicole;Kolle, Gabriel;Newell, Felicity;Pinese, Mark;Mead, R. Scott;Humphris, Jeremy L.;Kaplan, Warren;Jones, Marc D.;Colvin, Emily K.;Nagrial, Adnan M.;Humphrey, Emily S.;Chou, Angela;Chin, Venessa T.;Chantrill, Lorraine A.;Mawson, Amanda;Samra, Jaswinder S.;Kench, James G.;Lovell, Jessica A.;Daly, Roger J.;Merrett, Neil D.;Toon, Christopher;Epari, Krishna;Nguyen, Nam Q.;Barbour, Andrew;Zeps, Nikolajs;Kakkar, Nipun;Zhao, Fengmei;Wu, Yuan Qing;Wang, Min;Muzny, Donna M.;Fisher, William E.;Brunicardi, F. Charles;Hodges, Sally E.;Reid, Jeffrey G.;Drummond, Jennifer;Chang, Kyle;Han, Yi;Lewis, Lora R.;Dinh, Huyen;Buhay, Christian J.;Beck, Timothy;Timms, Lee;Sam, Michelle;Begley, Kimberly;Brown, Andrew;Pai, Deepa;Panchal, Ami;Buchner, Nicholas;De Borja, Richard;Denroche, Robert E.;Yung, Christina K.;Serra, Stefano;Onetto, Nicole;Mukhopadhyay, Debabrata;Tsao, Ming-Sound;Shaw, Patricia A.;Petersen, Gloria M.;Gallinger, Steven;Hruban, Ralph H.;Maitra, Anirban;Iacobuzio-Donahue, Christine A.;Schulick, Richard D.;Wolfgang, Christopher L.;Morgan, Richard A.;Lawlor, Rita T.;Capelli, Paola;Corbo, Vincenzo;Scardoni, Maria;Tortora, Giampaolo;Tempero, Margaret A.;Mann, Karen M.;Jenkins, Nancy A.;Perez-Mancera, Pedro A.;Adams, David J.;Largaespada, David A.;Wessels, Lodewyk F. A.;Rust, Alistair G.;Stein, Lincoln D.;Tuveson, David A.;Copeland, Neal G.;Musgrove, Elizabeth A.;Scarpa, Aldo;Eshleman, James R.;Hudson, Thomas J.;Sutherland, Robert L.;Wheeler, David A.;Pearson, John V.;McPherson, John D.;Gibbs, Richard A.;Grimmond, Sean M.
通讯作者：
Grimmond, Sean M.