RT Journal
A1 Berger, Michael F.
A1 Levin, Joshua Z.
A1 Vijayendran, Krishna
A1 Sivachenko, Andrey
A1 Adiconis, Xian
A1 Maguire, Jared
A1 Johnson, Laura A.
A1 Robinson, James
A1 Verhaak, Roel G.
A1 Sougnez, Carrie
A1 Onofrio, Robert C.
A1 Ziaugra, Liuda
A1 Cibulskis, Kristian
A1 Laine, Elisabeth
A1 Barretina, Jordi
A1 Winckler, Wendy
A1 Fisher, David E.
A1 Getz, Gad
A1 Meyerson, Matthew
A1 Jaffe, David B.
A1 Gabriel, Stacey B.
A1 Lander, Eric S.
A1 Dummer, Reinhard
A1 Gnirke, Andreas
A1 Nusbaum, Chad
A1 Garraway, Levi A.
T1 Integrative analysis of the melanoma transcriptome
JF Genome Research 
JO Genome Research 
YR 2010 
FD April 01 
VO 20 
IS 4 
SP 413 
OP 427 
DO 10.1101/gr.103697.109 
UL http://genome.cshlp.org/content/20/4/413.abstract 
AB 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.