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- Title
Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma.
- Authors
Nikolaev, Sergey I; Rimoldi, Donata; Iseli, Christian; Valsesia, Armand; Robyr, Daniel; Gehrig, Corinne; Harshman, Keith; Guipponi, Michel; Bukach, Olesya; Zoete, Vincent; Michielin, Olivier; Muehlethaler, Katja; Speiser, Daniel; Beckmann, Jacques S; Xenarios, Ioannis; Halazonetis, Thanos D; Jongeneel, C Victor; Stevenson, Brian J; Antonarakis, Stylianos E
- 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.
- Publication
Nature Genetics, 2012, Vol 44, Issue 2, p133
- ISSN
1061-4036
- Publication type
Academic Journal
- DOI
10.1038/ng.1026