Melanoma genome sequencing reveals frequent PREX2 mutations.
Melanoma genome sequencing reveals frequent PREX2 mutations.
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DOI：
10.1038/nature11071
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发表时间：
2012-05-09
期刊：
影响因子：
64.8
通讯作者：
Garraway, Levi A.
中科院分区：
文献类型：
--
作者：
Berger, Michael F.;Hodis, Eran;Heffernan, Timothy P.;Deribe, Yonathan Lissanu;Lawrence, Michael S.;Protopopov, Alexei;Ivanova, Elena;Watson, Ian R.;Nickerson, Elizabeth;Ghosh, Papia;Zhang, Hailei;Zeid, Rhamy;Ren, Xiaojia;Cibulskis, Kristian;Sivachenko, Andrey Y.;Wagle, Nikhil;Sucker, Antje;Sougnez, Carrie;Onofrio, Robert;Ambrogio, Lauren;Auclair, Daniel;Fennell, Timothy;Carter, Scott L.;Drier, Yotam;Stojanov, Petar;Singer, Meredith A.;Voet, Douglas;Jing, Rui;Saksena, Gordon;Barretina, Jordi;Ramos, Alex H.;Pugh, Trevor J.;Stransky, Nicolas;Parkin, Melissa;Winckler, Wendy;Mahan, Scott;Ardlie, Kristin;Baldwin, Jennifer;Wargo, Jennifer;Schadendorf, Dirk;Meyerson, Matthew;Gabriel, Stacey B.;Golub, Todd R.;Wagner, Stephan N.;Lander, Eric S.;Getz, Gad;Chin, Lynda;Garraway, Levi A.
黑色素瘤以其转移倾向、晚期环境中的致死性以及与生命早期的紫外线（UV）暴露相关而闻名。为了获得黑色素瘤的全面基因组视图，我们对25个转移性黑色素瘤的基因组和匹配的种系DNA进行了测序。观察到广泛的点突变率：在原发于四肢非紫外线暴露的无毛皮肤上的黑素瘤中最低（每Mb基因组3和14个），在那些起源于躯干有毛皮肤的黑素瘤中居中（范围=每Mb 5至55个），在有记录的慢性日光暴露史的患者中最高（每Mb 111个）。全基因组序列数据的分析确定PREX 2-一种PTEN相互作用蛋白和乳腺癌中PTEN的负调节因子-作为一种显著突变的基因，在107例人类黑色素瘤的独立扩展队列中突变频率约为14%。PREX 2突变是生物学相关的，因为突变PREX 2的异位表达加速了体内永生化人黑素细胞的肿瘤形成。因此，人类黑色素瘤肿瘤的全基因组测序揭示了紫外线发病机制的基因组证据，并发现了一个新的复发突变基因在黑色素瘤。
Melanoma is notable for its metastatic propensity, lethality in the advanced setting, and association with ultraviolet (UV) exposure early in life. To obtain a comprehensive genomic view of melanoma, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-UV exposed hairless skin of the extremities (3 and 14 per Mb genome), intermediate in those originating from hair-bearing skin of the trunk (range = 5 to 55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 - a PTEN-interacting protein and negative regulator of PTEN in breast cancer - as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumor formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumors revealed genomic evidence of UV pathogenesis and discovered a new recurrently mutated gene in melanoma.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
14.9
作者：
通讯作者：
--
影响因子：
64.8
作者：
通讯作者：
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影响因子：
64.5
作者：
Rausch T;Jones DT;Zapatka M;Stütz AM;Zichner T;Weischenfeldt J;Jäger N;Remke M;Shih D;Northcott PA;Pfaff E;Tica J;Wang Q;Massimi L;Witt H;Bender S;Pleier S;Cin H;Hawkins C;Beck C;von Deimling A;Hans V;Brors B;Eils R;Scheurlen W;Blake J;Benes V;Kulozik AE;Witt O;Martin D;Zhang C;Porat R;Merino DM;Wasserman J;Jabado N;Fontebasso A;Bullinger L;Rücker FG;Döhner K;Döhner H;Koster J;Molenaar JJ;Versteeg R;Kool M;Tabori U;Malkin D;Korshunov A;Taylor MD;Lichter P;Pfister SM;Korbel JO
通讯作者：
Korbel JO
影响因子：
14.9
作者：
Forbes, Simon A.;Tang, Gurpreet;Futreal, P. Andrew
通讯作者：
Futreal, P. Andrew