Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma

被引：148

作者：

Gartner, Jared J. ^{[1
]}

Parker, Stephen C. J. ^{[1
]}

Prickett, Todd D. ^{[1
]}

Dutton-Regester, Ken ^{[3
]}

Stitzel, Michael L. ^{[1
]}

Lin, Jimmy C. ^{[4
]}

Davis, Sean ^{[2
]}

Simhadri, Vijaya L. ^{[5
]}

Jha, Sujata ^{[6
,7
]}

Katagiri, Nobuko ^{[5
]}

Gotea, Valer ^{[1
]}

Teer, Jamie K. ^{[1
]}

Wei, Xiaomu ^{[1
]}

Morken, Mario A. ^{[1
]}

Bhanot, Umesh K. ^{[8
]}

Chen, Guo ^{[9
]}

Elnitski, Laura L. ^{[1
]}

Davies, Michael A. ^{[9
]}

Gershenwald, Jeffrey E. ^{[9
]}

Carter, Hannah ^{[10
]}

Karchin, Rachel ^{[10
]}

Robinson, William ^{[11
]}

Robinson, Steven ^{[11
]}

Rosenberg, Steven A. ^{[2
]}

Collins, Francis S. ^{[1
]}

Parmigiani, Giovanni ^{[12
,13
]}

Komar, Anton A. ^{[6
,7
]}

Kimchi-Sarfaty, Chava ^{[5
]}

Hayward, Nicholas K. ^{[3
]}

Margulies, Elliott H. ^{[1
,14
]}

Samuels, Yardena ^{[1
,15
]}

机构：

[1] NHGRI, Bethesda, MD 20892 USA

[2] NCI, NIH, Bethesda, MD 20892 USA

[3] Queensland Inst Med Res, Div Genet & Computat Biol, Brisbane, Qld 4006, Australia

[4] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA

[5] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA

[6] Cleveland State Univ, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA

[7] Cleveland State Univ, Dept Biol Geol & Environm Sci, Cleveland, OH 44115 USA

[8] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA

[10] Johns Hopkins Univ, Inst Computat Med, Dept Biomed Engn, Baltimore, MD 21218 USA

[11] Univ Colorado, Sch Med, Div Med Oncol, Aurora, CO 80045 USA

[12] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[13] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[14] Illumina United Kingdom, Saffron Walden CB10 1XL, Essex, England

[15] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 33期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

TERT PROMOTER MUTATIONS; POSITIVE SELECTION; REVEALS; CONSTRAINT; EVOLUTION; SUBSTRATE; GENE; SITE;

D O I：

10.1073/pnas.1304227110

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Synonymous mutations, which do not alter the protein sequence, have been shown to affect protein function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683-691]. However, synonymous mutations are rarely investigated in the cancer genomics field. We used whole-genome and -exome sequencing to identify somatic mutations in 29 melanoma samples. Validation of one synonymous somatic mutation in BCL2L12 in 285 samples identified 12 cases that harbored the recurrent F17F mutation. This mutation led to increased BCL2L12 mRNA and protein levels because of differential targeting of WT and mutant BCL2L12 by hsa-miR-671-5p. Protein made from mutant BCL2L12 transcript bound p53, inhibited UV-induced apoptosis more efficiently than WT BCL2L12, and reduced endogenous p53 target gene transcription. This report shows selection of a recurrent somatic synonymous mutation in cancer. Our data indicate that silent alterations have a role to play in human cancer, emphasizing the importance of their investigation in future cancer genome studies.

引用

页码：13481 / 13486

页数：6

共 35 条

[1]

Melanoma genome sequencing reveals frequent PREX2 mutations [J].

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. .

NATURE, 2012, 485 (7399) :502-506

[2]

A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn's disease [J].

Brest, Patrick ;

Lapaquette, Pierre ;

Souidi, Mouloud ;

Lebrigand, Kevin ;

Cesaro, Annabelle ;

Vouret-Craviari, Valerie ;

Mari, Bernard ;

Barbry, Pascal ;

Mosnier, Jean-Francois ;

Hebuterne, Xavier ;

Harel-Bellan, Annick ;

Mograbi, Baharia ;

Darfeuille-Michaud, Arlette ;

Hofman, Paul .

NATURE GENETICS, 2011, 43 (03) :242-U24

[3]

Hearing silence: non-neutral evolution at synonymous sites in mammals [J].

Chamary, JV ;

Parmley, JL ;

Hurst, LD .

NATURE REVIEWS GENETICS, 2006, 7 (02) :98-108

[4]

Distribution and intensity of constraint in mammalian genomic sequence [J].

Cooper, GM ;

Stone, EA ;

Asimenos, G ;

Green, ED ;

Batzoglou, S ;

Sidow, A .

GENOME RESEARCH, 2005, 15 (07) :901-913

[5]

Mutations of the BRAF gene in human cancer [J].

Davies, H ;

Bignell, GR ;

Cox, C ;

Stephens, P ;

Edkins, S ;

Clegg, S ;

Teague, J ;

Woffendin, H ;

Garnett, MJ ;

Bottomley, W ;

Davis, N ;

Dicks, N ;

Ewing, R ;

Floyd, Y ;

Gray, K ;

Hall, S ;

Hawes, R ;

Hughes, J ;

Kosmidou, V ;

Menzies, A ;

Mould, C ;

Parker, A ;

Stevens, C ;

Watt, S ;

Hooper, S ;

Wilson, R ;

Jayatilake, H ;

Gusterson, BA ;

Cooper, C ;

Shipley, J ;

Hargrave, D ;

Pritchard-Jones, K ;

Maitland, N ;

Chenevix-Trench, G ;

Riggins, GJ ;

Bigner, DD ;

Palmieri, G ;

Cossu, A ;

Flanagan, A ;

Nicholson, A ;

Ho, JWC ;

Leung, SY ;

Yuen, ST ;

Weber, BL ;

Siegler, HF ;

Darrow, TL ;

Paterson, H ;

Marais, R ;

Marshall, CJ ;

Wooster, R .

NATURE, 2002, 417 (6892) :949-954

[6]

Identifying a High Fraction of the Human Genome to be under Selective Constraint Using GERP plus [J].

Davydov, Eugene V. ;

Goode, David L. ;

Sirota, Marina ;

Cooper, Gregory M. ;

Sidow, Arend ;

Batzoglou, Serafim .

PLOS COMPUTATIONAL BIOLOGY, 2010, 6 (12)

[7]

EPS8, A SUBSTRATE FOR THE EPIDERMAL GROWTH-FACTOR RECEPTOR KINASE, ENHANCES EGF-DEPENDENT MITOGENIC SIGNALS [J].

FAZIOLI, F ;

MINICHIELLO, L ;

MATOSKA, V ;

CASTAGNINO, P ;

MIKI, T ;

WONG, WT ;

DIFIORE, PP .

EMBO JOURNAL, 1993, 12 (10) :3799-3808

[8]

Evolutionary constraint facilitates interpretation of genetic variation in resequenced human genomes [J].

Goode, David L. ;

Cooper, Gregory M. ;

Schmutz, Jeremy ;

Dickson, Mark ;

Gonzales, Eidelyn ;

Tsai, Ming ;

Karra, Kalpana ;

Davydov, Eugene ;

Batzoglou, Serafim ;

Myers, Richard M. ;

Sidow, Arend .

GENOME RESEARCH, 2010, 20 (03) :301-310

[9]

Patterns of somatic mutation in human cancer genomes [J].

Greenman, Christopher ;

Stephens, Philip ;

Smith, Raffaella ;

Dalgliesh, Gillian L. ;

Hunter, Christopher ;

Bignell, Graham ;

Davies, Helen ;

Teague, Jon ;

Butler, Adam ;

Edkins, Sarah ;

O'Meara, Sarah ;

Vastrik, Imre ;

Schmidt, Esther E. ;

Avis, Tim ;

Barthorpe, Syd ;

Bhamra, Gurpreet ;

Buck, Gemma ;

Choudhury, Bhudipa ;

Clements, Jody ;

Cole, Jennifer ;

Dicks, Ed ;

Forbes, Simon ;

Gray, Kris ;

Halliday, Kelly ;

Harrison, Rachel ;

Hills, Katy ;

Hinton, Jon ;

Jenkinson, Andy ;

Jones, David ;

Menzies, Andy ;

Mironenko, Tatiana ;

Perry, Janet ;

Raine, Keiran ;

Richardson, Dave ;

Shepherd, Rebecca ;

Small, Alexandra ;

Tofts, Calli ;

Varian, Jennifer ;

Webb, Tony ;

West, Sofie ;

Widaa, Sara ;

Yates, Andy ;

Cahill, Daniel P. ;

Louis, David N. ;

Goldstraw, Peter ;

Nicholson, Andrew G. ;

Brasseur, Francis ;

Looijenga, Leendert ;

Weber, Barbara L. ;

Chiew, Yoke-Eng .

NATURE, 2007, 446 (7132) :153-158

[10]

A Landscape of Driver Mutations in Melanoma [J].

Hodis, Eran ;

Watson, Ian R. ;

Kryukov, Gregory V. ;

Arold, Stefan T. ;

Imielinski, Marcin ;

Theurillat, Jean-Philippe ;

Nickerson, Elizabeth ;

Auclair, Daniel ;

Li, Liren ;

Place, Chelsea ;

DiCara, Daniel ;

Ramos, Alex H. ;

Lawrence, Michael S. ;

Cibulskis, Kristian ;

Sivachenko, Andrey ;

Voet, Douglas ;

Saksena, Gordon ;

Stransky, Nicolas ;

Onofrio, Robert C. ;

Winckler, Wendy ;

Ardlie, Kristin ;

Wagle, Nikhil ;

Wargo, Jennifer ;

Chong, Kelly ;

Morton, Donald L. ;

Stemke-Hale, Katherine ;

Chen, Guo ;

Noble, Michael ;

Meyerson, Matthew ;

Ladbury, John E. ;

Davies, Michael A. ;

Gershenwald, Jeffrey E. ;

Wagner, Stephan N. ;

Hoon, Dave S. B. ;

Schadendorf, Dirk ;

Lander, Eric S. ;

Gabriel, Stacey B. ;

Getz, Gad ;

Garraway, Levi A. ;

Chin, Lynda .

CELL, 2012, 150 (02) :251-263

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