Scientific Publications

Modeling genomic diversity and tumor dependency in malignant melanoma.

Publication TypeJournal Article
AuthorsLin, WM, Baker AC, Beroukhim R., Winckler W., Feng W., Marmion JM, Laine E., Greulich H., Tseng H., Gates C., Hodi FS, Dranoff G., Sellers WR, Thomas RK, Meyerson M., Golub T. R., Dummer R., Herlyn M., Getz G., and Garraway LA
AbstractThe classification of human tumors based on molecular criteria offers tremendous clinical potential; however, discerning critical and "druggable" effectors on a large scale will also require robust experimental models reflective of tumor genomic diversity. Here, we describe a comprehensive genomic analysis of 101 melanoma short-term cultures and cell lines. Using an analytic approach designed to enrich for putative "driver" events, we show that cultured melanoma cells encompass the spectrum of significant genomic alterations present in primary tumors. When annotated according to these lesions, melanomas cluster into subgroups suggestive of distinct oncogenic mechanisms. Integrating gene expression data suggests novel candidate effector genes linked to recurrent copy gains and losses, including both phosphatase and tensin homologue (PTEN)-dependent and PTEN-independent tumor suppressor mechanisms associated with chromosome 10 deletions. Finally, sample-matched pharmacologic data show that FGFR1 mutations and extracellular signal-regulated kinase (ERK) activation may modulate sensitivity to mitogen-activated protein kinase/ERK kinase inhibitors. Genetically defined cell culture collections therefore offer a rich framework for systematic functional studies in melanoma and other tumors.
Year of Publication2008
JournalCancer research
Volume68
Issue3
Pages664-73
Date Published (YYYY/MM/DD)2008/02/01
ISSN Number0008-5472
DOI10.1158/0008-5472.CAN-07-2615
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/18245465?dopt=Abstract