Transcriptional consequences of genomic structural aberrations in breast cancer

被引：59

作者：

Inaki, Koichiro ^{[1
]}

Hillmer, Axel M. ^{[1
]}

Ukil, Leena ^{[1
]}

Yao, Fei ^{[1
,2
]}

Woo, Xing Yi ^{[1
]}

Vardy, Leah A. ^{[3
]}

Zawack, Kelson Folkvard Braaten ^{[1
]}

Lee, Charlie Wah Heng ^{[1
]}

Ariyaratne, Pramila Nuwantha ^{[1
]}

Chan, Yang Sun ^{[1
]}

Desai, Kartiki Vasant ^{[1
]}

Bergh, Jonas ^{[4
]}

Hall, Per ^{[5
]}

Putti, Thomas Choudary ^{[6
]}

Ong, Wai Loon ^{[1
]}

Shahab, Atif ^{[1
]}

Cacheux-Rataboul, Valere ^{[1
]}

Karuturi, Radha Krishna Murthy ^{[1
]}

Sung, Wing-Kin ^{[1
]}

Ruan, Xiaoan ^{[1
]}

Bourque, Guillaume ^{[1
]}

Ruan, Yijun ^{[1
]}

Liu, Edison T. ^{[1
]}

机构：

[1] Genome Inst Singapore, Singapore 138672, Singapore

[2] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol & Publ Hlth, Singapore 117597, Singapore

[3] Inst Med Biol, Singapore 138648, Singapore

[4] Karolinska Inst, Dept Oncol Pathol, SE-17177 Stockholm, Sweden

[5] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden

[6] Natl Univ Singapore, Dept Pathol, Singapore 119077, Singapore

来源：

GENOME RESEARCH | 2011年 / 21卷 / 05期

关键词：

GENE FUSIONS; PROSTATE-CANCER; LUNG-CANCER; METASTASIS; COMPLEX; TRANSLOCATIONS; OVEREXPRESSION; REARRANGEMENT; DEREGULATION; TRANSLATION;

D O I：

10.1101/gr.113225.110

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Using a long-span, paired-end deep sequencing strategy, we have comprehensively identified cancer genome rearrangements in eight breast cancer genomes. Herein, we show that 40%-54% of these structural genomic rearrangements result in different forms of fusion transcripts and that 44% are potentially translated. We find that single segmental tandem duplication spanning several genes is a major source of the fusion gene transcripts in both cell lines and primary tumors involving adjacent genes placed in the reverse-order position by the duplication event. Certain other structural mutations, however, tend to attenuate gene expression. From these candidate gene fusions, we have found a fusion transcript (RPS6KB1-VMP1) recurrently expressed in similar to 30% of breast cancers associated with potential clinical consequences. This gene fusion is caused by tandem duplication on 17q23 and appears to be an indicator of local genomic instability altering the expression of oncogenic components such as MIR21 and RPS6KB1.

引用

页码：676 / 687

页数：12

共 44 条

[1] Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis [J].

Bärlund, M ;

Forozan, F ;

Kononen, J ;

Bubendorf, L ;

Chen, YD ;

Bittner, ML ;

Torhorst, J ;

Haas, P ;

Bucher, C ;

Sauter, G ;

Kallioniemi, OP ;

Kallioniemi, A .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (15) :1252-1259

[2] Cloning of BCAS3 (17q23) and BCAS4 (20q13) genes that undergo amplification, overexpression, and fusion in breast cancer [J].

Bärlund, M ;

Monni, O ;

Weaver, JD ;

Kauraniemi, P ;

Sauter, G ;

Heiskanen, M ;

Kallioniemi, OP ;

Kallioniemi, A .

GENES CHROMOSOMES & CANCER, 2002, 35 (04) :311-317

[3] Evaluation of paired-end sequencing strategies for detection of genome rearrangements in cancer [J].

Bashir, Ali ;

Volik, Stanislav ;

Collins, Colin ;

Bafna, Vineet ;

Raphael, Benjamin J. .

PLOS COMPUTATIONAL BIOLOGY, 2008, 4 (04)

[4]

Beilharz Traude H., 2004, Briefings in Functional Genomics & Proteomics, V3, P103, DOI 10.1093/bfgp/3.2.103

[5] The landscape of somatic copy-number alteration across human cancers [J].

Beroukhim, Rameen ;

Mermel, Craig H. ;

Porter, Dale ;

Wei, Guo ;

Raychaudhuri, Soumya ;

Donovan, Jerry ;

Barretina, Jordi ;

Boehm, Jesse S. ;

Dobson, Jennifer ;

Urashima, Mitsuyoshi ;

Mc Henry, Kevin T. ;

Pinchback, Reid M. ;

Ligon, Azra H. ;

Cho, Yoon-Jae ;

Haery, Leila ;

Greulich, Heidi ;

Reich, Michael ;

Winckler, Wendy ;

Lawrence, Michael S. ;

Weir, Barbara A. ;

Tanaka, Kumiko E. ;

Chiang, Derek Y. ;

Bass, Adam J. ;

Loo, Alice ;

Hoffman, Carter ;

Prensner, John ;

Liefeld, Ted ;

Gao, Qing ;

Yecies, Derek ;

Signoretti, Sabina ;

Maher, Elizabeth ;

Kaye, Frederic J. ;

Sasaki, Hidefumi ;

Tepper, Joel E. ;

Fletcher, Jonathan A. ;

Tabernero, Josep ;

Baselga, Jose ;

Tsao, Ming-Sound ;

Demichelis, Francesca ;

Rubin, Mark A. ;

Janne, Pasi A. ;

Daly, Mark J. ;

Nucera, Carmelo ;

Levine, Ross L. ;

Ebert, Benjamin L. ;

Gabriel, Stacey ;

Rustgi, Anil K. ;

Antonescu, Cristina R. ;

Ladanyi, Marc ;

Letai, Anthony .

NATURE, 2010, 463 (7283) :899-905

[6] The Dbl family of oncogenes [J].

Cerione, RA ;

Zheng, Y .

CURRENT OPINION IN CELL BIOLOGY, 1996, 8 (02) :216-222

[7] DEP domains: More than just membrane anchors [J].

Chen, Songhai ;

Hamm, Heidi E. .

DEVELOPMENTAL CELL, 2006, 11 (04) :436-438

[8] Role of the TMPRSS2-ERG gene fusion in prostate cancer [J].

Chinnaiyan, Arul M. .

NEOPLASIA, 2008, 10 (02) :177-U23

[9] An oestrogen-receptor-α-bound human chromatin interactome [J].

Fullwood, Melissa J. ;

Liu, Mei Hui ;

Pan, You Fu ;

Liu, Jun ;

Xu, Han ;

Bin Mohamed, Yusoff ;

Orlov, Yuriy L. ;

Velkov, Stoyan ;

Ho, Andrea ;

Mei, Poh Huay ;

Chew, Elaine G. Y. ;

Huang, Phillips Yao Hui ;

Welboren, Willem-Jan ;

Han, Yuyuan ;

Ooi, Hong Sain ;

Ariyaratne, Pramila N. ;

Vega, Vinsensius B. ;

Luo, Yanquan ;

Tan, Peck Yean ;

Choy, Pei Ye ;

Wansa, K. D. Senali Abayratna ;

Zhao, Bing ;

Lim, Kar Sian ;

Leow, Shi Chi ;

Yow, Jit Sin ;

Joseph, Roy ;

Li, Haixia ;

Desai, Kartiki V. ;

Thomsen, Jane S. ;

Lee, Yew Kok ;

Karuturi, R. Krishna Murthy ;

Herve, Thoreau ;

Bourque, Guillaume ;

Stunnenberg, Hendrik G. ;

Ruan, Xiaoan ;

Cacheux-Rataboul, Valere ;

Sung, Wing-Kin ;

Liu, Edison T. ;

Wei, Chia-Lin ;

Cheung, Edwin ;

Ruan, Yijun .

NATURE, 2009, 462 (7269) :58-64

[10] Finding fusion genes resulting from chromosome rearrangement by analyzing the expressed sequence databases [J].

Hahn, Y ;

Bera, TK ;

Gehlhaus, K ;

Kirsch, IR ;

Pastan, IH ;

Lee, B .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (36) :13257-13261

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