The topography of mutational processes in breast cancer genomes

被引：193

作者：

Morganella, Sandro ^{[1
]}

Alexandrov, Ludmil B. ^{[2
,3
,4
]}

Glodzik, Dominik ^{[2
]}

Zou, Xueqing ^{[2
]}

Davies, Helen ^{[2
]}

Staaf, Johan ^{[5
]}

Sieuwerts, Anieta M. ^{[6
,7
]}

Brinkman, Arie B. ^{[8
]}

Martin, Sancha ^{[2
]}

Ramakrishna, Manasa ^{[2
]}

Butler, Adam ^{[2
]}

Kim, Hyung-Yong ^{[9
]}

Borg, Ake ^{[5
]}

Sotiriou, Christos ^{[10
]}

Futreal, P. Andrew ^{[1
,11
]}

Campbell, Peter J. ^{[2
]}

Span, Paul N. ^{[12
,13
]}

Van Laere, Steven ^{[14
,15
]}

Lakhani, Sunil R. ^{[16
,17
,18
]}

Eyfjord, Jorunn E. ^{[19
]}

Thompson, Alastair M. ^{[20
,21
]}

Stunnenberg, Hendrik G.

de Vijver, Marc J. van ^{[22
]}

Martens, John W. M. ^{[6
,7
]}

Borresen-Dale, Anne-Lise ^{[23
,24
]}

Richardson, Andrea L. ^{[25
,26
]}

Kong, Gu ^{[9
]}

Thomas, Gilles ^{[27
]}

Sale, Julian ^{[28
]}

Rada, Cristina ^{[28
]}

Stratton, Michael R. ^{[2
]}

Birney, Ewan ^{[1
]}

Nik-Zainal, Serena ^{[2
,29
]}

机构：

[1] European Bioinformat Inst, European Mol Biol Lab, Wellcome Trust Genome Campus, Hinxton CB10 1SD, Cambs, England

[2] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

[3] Los Alamos Natl Lab, Theoret Biol & Biophys T 6, Los Alamos, NM 87545 USA

[4] Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA

[5] Lund Univ, Div Oncol & Pathol, Dept Clin Sci Lund, SE-22381 Lund, Sweden

[6] Erasmus Univ, Dept Med Oncol, Erasmus MC Canc Inst, Med Ctr, NL-3015 CN Rotterdam, Netherlands

[7] Erasmus Univ, Canc Genom Netherlands, NL-3015 CN Rotterdam, Netherlands

[8] Radboud Univ Nijmegen, Fac Sci, Dept Mol Biol, NL-6525 GA Nijmegen, Netherlands

[9] Hanyang Univ, Dept Pathol, Coll Med, Seoul 133791, South Korea

[10] Univ Libre Bruxelles, Breast Canc Translat Res Lab, Inst Jules Bordet, Bd Waterloo 121, B-1000 Brussels, Belgium

[11] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77230 USA

[12] Radboud Univ Nijmegen, Med Ctr, Dept Radiat Oncol, NL-6525 GA Nijmegen, Netherlands

[13] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, NL-6525 GA Nijmegen, Netherlands

[14] GZA Hosp Sint Augustinus, Translat Canc Res Unit, Antwerp, Belgium

[15] Univ Antwerp, Oncol Res Ctr, B-2610 Antwerp, Belgium

[16] Univ Queensland, Ctr Clin Res, Brisbane, Qld 4059, Australia

[17] Univ Queensland, Sch Med, Brisbane, Qld 4059, Australia

[18] Royal Brisbane & Womens Hosp, Pathol Queensland, Brisbane, Qld, Australia

[19] Univ Iceland, Fac Med, Canc Res Lab, IS-101 Reykjavik, Iceland

[20] MD Anderson Canc Res Ctr, Dept Breast Surg Oncol, 1400 Pressler St, Houston, TX 77030 USA

[21] Univ Dundee, Dept Surg Oncol, Dundee DD1 9SY, Scotland

[22] Univ Amsterdam, Acad Med Ctr, Dept Pathol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[23] Norwegian Radium Hosp, Oslo Univ Hosp, Dept Canc Genet, Inst Canc Res, N-0310 Oslo, Norway

[24] Univ Oslo, KG Jebsen Ctr Breast Canc Res, Inst Clin Med, N-0310 Oslo, Norway

[25] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[26] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[27] Synergie Lyon Canc, Ctr Leon Berard, 28 Rue Laennec, Lyon 08, France

[28] MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England

[29] Cambridge Univ Hosp NHS Fdn Trust, East Anglian Med Genet Serv, Cambridge CB2 9NB, England

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

新加坡国家研究基金会; 欧盟第七框架计划; 美国能源部; 英国惠康基金;

关键词：

MISMATCH REPAIR; CHROMATIN ORGANIZATION; ABASIC SITE; MATING-TYPE; DNA-REPAIR; SIGNATURES; INSTABILITY; LANDSCAPE; PATTERNS; APOBEC3A;

D O I：

10.1038/ncomms11383

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：

Somatic mutations in human cancers show unevenness in genomic distribution that correlate with aspects of genome structure and function. These mutations are, however, generated by multiple mutational processes operating through the cellular lineage between the fertilized egg and the cancer cell, each composed of specific DNA damage and repair components and leaving its own characteristic mutational signature on the genome. Using somatic mutation catalogues from 560 breast cancer whole-genome sequences, here we show that each of 12 base substitution, 2 insertion/deletion (indel) and 6 rearrangement mutational signatures present in breast tissue, exhibit distinct relationships with genomic features relating to transcription, DNA replication and chromatin organization. This signature-based approach permits visualization of the genomic distribution of mutational processes associated with APOBEC enzymes, mismatch repair deficiency and homologous recombinational repair deficiency, as well as mutational processes of unknown aetiology. Furthermore, it highlights mechanistic insights including a putative replication-dependent mechanism of APOBEC-related mutagenesis.

引用

页数：11

共 53 条

[1]

Genome instability:: a mechanistic view of its causes and consequences [J].