Quick Search:

is currently disabled due to reindexing of the ZORA database. Please use Advanced Search.
uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-13925

Lin, W M; Baker, A C; Beroukhim, R; Winckler, W; Feng, W; Marmion, J M; Laine, E; Greulich, H; Tseng, H; Gates, C; Hodi, F S; Dranoff, G; Sellers, W R; Thomas, R K; Meyerson, M; Golub, T R; Dummer, R; Herlyn, M; Getz, G; Garraway, L A (2008). Modeling genomic diversity and tumor dependency in malignant melanoma. Cancer Research, 68(3):664-673.

[img]Accepted Version
PDF
126kB
[img] PDF - Registered users only
2MB

Abstract

The 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.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
DDC:610 Medicine & health
Language:English
Date:February 2008
Deposited On:18 Feb 2009 16:09
Last Modified:27 Nov 2013 16:41
Publisher:American Association for Cancer Research
ISSN:0008-5472
Publisher DOI:10.1158/0008-5472.CAN-07-2615
PubMed ID:18245465
Citations:Web of Science®. Times Cited: 131
Google Scholar™
Scopus®. Citation Count: 133

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page