Scientific Publications

Integrative analysis of the melanoma transcriptome.

Publication TypeJournal Article
AuthorsBerger, MF, Levin JZ, Vijayendran K., Sivachenko A., Adiconis X., Maguire J., Johnson LA, Robinson J., Verhaak RG, Sougnez C., Onofrio RC, Ziaugra L., Cibulskis K., Laine E., Barretina J., Winckler W., Fisher DE, Getz G., Meyerson M., Jaffe DB, Gabriel SB, Lander E. S., Dummer R., Gnirke A., Nusbaum C., and Garraway LA
AbstractGlobal 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.
Year of Publication2010
JournalGenome research
Volume20
Issue4
Pages413-27
Date Published (YYYY/MM/DD)2010/04/01
ISSN Number1088-9051
DOI10.1101/gr.103697.109
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/20179022?dopt=Abstract