|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
3
|
|
pubmed:dateCreated |
2008-2-4
|
|
pubmed:abstractText |
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.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/FGFR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Fibroblast Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/raf Kinases
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
1538-7445
|
|
pubmed:author |
pubmed-author:BakerAlissa CAC,
pubmed-author:BeroukhimRameenR,
pubmed-author:DranoffGlennG,
pubmed-author:DummerReinhardR,
pubmed-author:FengWheiW,
pubmed-author:GarrawayLevi ALA,
pubmed-author:GatesCaseyC,
pubmed-author:GetzGadG,
pubmed-author:GolubTodd RTR,
pubmed-author:GreulichHeidiH,
pubmed-author:HerlynMeenhardM,
pubmed-author:HodiF StephenFS,
pubmed-author:LaineElisabethE,
pubmed-author:LinWilliam MWM,
pubmed-author:MarmionJennifer MJM,
pubmed-author:MeyersonMatthewM,
pubmed-author:SellersWilliam RWR,
pubmed-author:ThomasRoman KRK,
pubmed-author:TsengHsiuyiH,
pubmed-author:WincklerWendyW
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
1
|
|
pubmed:volume |
68
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
664-73
|
|
pubmed:dateRevised |
2011-4-15
|
|
pubmed:meshHeading |
pubmed-meshheading:18245465-Algorithms,
pubmed-meshheading:18245465-Cell Line, Tumor,
pubmed-meshheading:18245465-Chromosome Aberrations,
pubmed-meshheading:18245465-Chromosome Deletion,
pubmed-meshheading:18245465-Chromosomes, Human, Pair 10,
pubmed-meshheading:18245465-Cluster Analysis,
pubmed-meshheading:18245465-DNA, Neoplasm,
pubmed-meshheading:18245465-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:18245465-Gene Expression Profiling,
pubmed-meshheading:18245465-Humans,
pubmed-meshheading:18245465-Loss of Heterozygosity,
pubmed-meshheading:18245465-Melanoma,
pubmed-meshheading:18245465-Mitogen-Activated Protein Kinases,
pubmed-meshheading:18245465-PTEN Phosphohydrolase,
pubmed-meshheading:18245465-Polymorphism, Single Nucleotide,
pubmed-meshheading:18245465-Receptor, Fibroblast Growth Factor, Type 1,
pubmed-meshheading:18245465-raf Kinases
|
|
pubmed:year |
2008
|
|
pubmed:articleTitle |
Modeling genomic diversity and tumor dependency in malignant melanoma.
|
|
pubmed:affiliation |
Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
