Germline and somatic polymerase ε and δ mutations define a new class of hypermutated colorectal and endometrial cancers.
Germline and somatic polymerase ε and δ mutations define a new class of hypermutated colorectal and endometrial cancers.
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DOI：
10.1002/path.4185
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发表时间：
2013-06
影响因子：
7.3
通讯作者：
Tomlinson, Ian
中科院分区：
文献类型：
--
作者：
Briggs, Sarah;Tomlinson, Ian
关键词：
聚合酶ε和δ是复制真核生物DNA的主要酶。准确的复制通过沃森 - 克里克碱基配对以及聚合酶的核酸外切酶（校对）结构域的作用而实现。我们最近发现，POLE和POLD1的种系核酸外切酶结构域突变（EDMs）使患多发性结直肠腺瘤和癌（CRC）的风险增高。POLD1突变还使个体易患子宫内膜癌（EC）。这些突变具有高外显率和显性遗传的特点，尽管表型可能存在差异。我们将这种情况命名为聚合酶校对相关息肉病（PPAP）。在散发性CRC和EC中也发现了体细胞POLE EDMs，尽管检测到的体细胞POLD1 EDMs极少。种系和体细胞DNA聚合酶EDMs都会导致一种“超突变”的、显然是微卫星稳定的癌症类型，有时每个肿瘤会出现超过一百万个碱基替换。在此，我们提供证据表明POLE和POLD1是CRC和EC发病机制的重要促成因素，并强调了这一新兴领域的一些关键问题。版权所有© 2013英国和爱尔兰病理学会。由约翰威立父子有限公司出版
Polymerases ϵ and δ are the main enzymes that replicate eukaryotic DNA. Accurate replication occurs through Watson–Crick base pairing and also through the action of the polymerases' exonuclease (proofreading) domains. We have recently shown that germline exonuclease domain mutations (EDMs) of POLE and POLD1 confer a high risk of multiple colorectal adenomas and carcinoma (CRC). POLD1 mutations also predispose to endometrial cancer (EC). These mutations are associated with high penetrance and dominant inheritance, although the phenotype can be variable. We have named the condition polymerase proofreading-associated polyposis (PPAP). Somatic POLE EDMs have also been found in sporadic CRCs and ECs, although very few somatic POLD1 EDMs have been detected. Both the germline and the somatic DNA polymerase EDMs cause an ‘ultramutated’, apparently microsatellite-stable, type of cancer, sometimes leading to over a million base substitutions per tumour. Here, we present the evidence for POLE and POLD1 as important contributors to the pathogenesis of CRC and EC, and highlight some of the key questions in this emerging field. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
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影响因子：
64.8
作者：
Seshagiri, Somasekar;Stawiski, Eric W.;Durinck, Steffen;Modrusan, Zora;Storm, Elaine E.;Conboy, Caitlin B.;Chaudhuri, Subhra;Guan, Yinghui;Janakiraman, Vasantharajan;Jaiswal, Bijay S.;Guillory, Joseph;Ha, Connie;Dijkgraaf, Gerrit J. P.;Stinson, Jeremy;Gnad, Florian;Huntley, Melanie A.;Degenhardt, Jeremiah D.;Haverty, Peter M.;Bourgon, Richard;Wang, Weiru;Koeppen, Hartmut;Gentleman, Robert;Starr, Timothy K.;Zhang, Zemin;Largaespada, David A.;Wu, Thomas D.;de Sauvage, Frederic J.
通讯作者：
de Sauvage, Frederic J.
影响因子：
30.8
作者：
Dunlop MG;Dobbins SE;Farrington SM;Jones AM;Palles C;Whiffin N;Tenesa A;Spain S;Broderick P;Ooi LY;Domingo E;Smillie C;Henrion M;Frampton M;Martin L;Grimes G;Gorman M;Semple C;Ma YP;Barclay E;Prendergast J;Cazier JB;Olver B;Penegar S;Lubbe S;Chander I;Carvajal-Carmona LG;Ballereau S;Lloyd A;Vijayakrishnan J;Zgaga L;Rudan I;Theodoratou E;Colorectal Tumour Gene Identification (CORGI) Consortium;Starr JM;Deary I;Kirac I;Kovacević D;Aaltonen LA;Renkonen-Sinisalo L;Mecklin JP;Matsuda K;Nakamura Y;Okada Y;Gallinger S;Duggan DJ;Conti D;Newcomb P;Hopper J;Jenkins MA;Schumacher F;Casey G;Easton D;Shah M;Pharoah P;Lindblom A;Liu T;Swedish Low-Risk Colorectal Cancer Study Group;Smith CG;West H;Cheadle JP;COIN Collaborative Group;Midgley R;Kerr DJ;Campbell H;Tomlinson IP;Houlston RS
通讯作者：
Houlston RS
DOI：
10.1073/pnas.88.21.9473
发表时间：
1991-11-01
影响因子：
11.1
作者：
MORRISON, A;BELL, JB;SUGINO, A
通讯作者：
SUGINO, A
影响因子：
7.3
作者：
Donehower, Lawrence A.;Creighton, Chad J.;Schultz, Nikolaus;Shinbrot, Eve;Chang, Kyle;Gunaratne, Preethi H.;Muzny, Donna;Sander, Chris;Hamilton, Stanley R.;Gibbs, Richard A.;Wheeler, David
通讯作者：
Wheeler, David
影响因子：
11.4
作者：
MORRISON, A;JOHNSON, AL;SUGINO, A
通讯作者：
SUGINO, A