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Nat Genet. 2011 Dec 25;44(2):133-9. doi: 10.1038/ng.1026.

Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma.

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  • 1Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.

Abstract

We performed exome sequencing to detect somatic mutations in protein-coding regions in seven melanoma cell lines and donor-matched germline cells. All melanoma samples had high numbers of somatic mutations, which showed the hallmark of UV-induced DNA repair. Such a hallmark was absent in tumor sample-specific mutations in two metastases derived from the same individual. Two melanomas with non-canonical BRAF mutations harbored gain-of-function MAP2K1 and MAP2K2 (MEK1 and MEK2, respectively) mutations, resulting in constitutive ERK phosphorylation and higher resistance to MEK inhibitors. Screening a larger cohort of individuals with melanoma revealed the presence of recurring somatic MAP2K1 and MAP2K2 mutations, which occurred at an overall frequency of 8%. Furthermore, missense and nonsense somatic mutations were frequently found in three candidate melanoma genes, FAT4, LRP1B and DSC1.

PMID:
22197931
[PubMed - indexed for MEDLINE]
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