Integrative analysis of the melanoma transcriptome

被引：208

作者：

Berger, Michael F. ^{[1
]}

Levin, Joshua Z. ^{[1
]}

Vijayendran, Krishna ^{[1
,2
]}

Sivachenko, Andrey ^{[1
]}

Adiconis, Xian ^{[1
]}

Maguire, Jared ^{[1
]}

Johnson, Laura A. ^{[1
,2
]}

Robinson, James ^{[1
]}

Verhaak, Roel G. ^{[1
,2
]}

Sougnez, Carrie ^{[1
]}

Onofrio, Robert C. ^{[1
]}

Ziaugra, Liuda ^{[1
]}

Cibulskis, Kristian ^{[1
]}

Laine, Elisabeth ^{[3
]}

Barretina, Jordi ^{[1
]}

Winckler, Wendy ^{[1
]}

Fisher, David E. ^{[4
,5
,6
]}

Getz, Gad ^{[1
]}

Meyerson, Matthew ^{[1
,2
,7
]}

Jaffe, David B. ^{[1
]}

Gabriel, Stacey B. ^{[1
]}

Lander, Eric S. ^{[1
,8
,9
]}

Dummer, Reinhard ^{[3
]}

Gnirke, Andreas ^{[1
]}

Nusbaum, Chad ^{[1
]}

Garraway, Levi A. ^{[1
,2
,7
]}

机构：

[1] MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA

[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[3] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland

[4] Massachusetts Gen Hosp, Dept Dermatol & Cutaneous Biol, Res Ctr, Boston, MA 02114 USA

[5] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02199 USA

[6] Childrens Hosp, Boston, MA 02199 USA

[7] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA

[8] MIT, Dept Biol, Cambridge, MA 02142 USA

[9] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

来源：

GENOME RESEARCH | 2010年 / 20卷 / 04期

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; CHRONIC MYELOGENOUS LEUKEMIA; GENE FUSIONS; MULTIPLEX AMPLIFICATION; MALIGNANT-MELANOMA; GENOMIC ANALYSES; LUNG-CANCER; RNA-SEQ; MUTATIONS; IDENTIFICATION;

D O I：

10.1101/gr.103697.109

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：

Global studies of transcript structure and abundance in cancer cells enable the systematic discovery of aberrations that contribute to carcinogenesis, including gene fusions, alternative splice isoforms, and somatic mutations. We developed a systematic approach to characterize the spectrum of cancer-associated mRNA alterations through integration of transcriptomic and structural genomic data, and we applied this approach to generate new insights into melanoma biology. Using paired-end massively parallel sequencing of cDNA (RNA-seq) together with analyses of high-resolution chromosomal copy number data, we identified 11 novel melanoma gene fusions produced by underlying genomic rearrangements, as well as 12 novel readthrough transcripts. We mapped these chimeric transcripts to base-pair resolution and traced them to their genomic origins using matched chromosomal copy number information. We also used these data to discover and validate base-pair mutations that accumulated in these melanomas, revealing a surprisingly high rate of somatic mutation and lending support to the notion that point mutations constitute the major driver of melanoma progression. Taken together, these results may indicate new avenues for target discovery in melanoma, while also providing a template for large-scale transcriptome studies across many tumor types.

引用

页码：413 / 427

页数：15

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