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Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma

Rimoldi, Donata
Iseli, Christian
Valsesia, Armand
Harshman, Keith
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Published in Nature genetics. 2012, vol. 44, no. 2, p. 133-9
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.
Keywords Base SequenceCadherins/geneticsCell Line, TumorCohort StudiesDNA Repair/geneticsDesmocollinsExome/geneticsHumansMAP Kinase Kinase 1/antagonists & inhibitors/geneticsMAP Kinase Kinase 2/antagonists & inhibitors/geneticsMelanoma/geneticsMitogen-Activated Protein Kinase 1/geneticsMolecular Sequence DataMutationProto-Oncogene Proteins B-raf/geneticsReceptors, LDL/geneticsSkin Neoplasms/geneticsTumor Suppressor Proteins/geneticsUltraviolet Rays/adverse effects
PMID: 22197931
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Research group Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248)
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NIKOLAEV, Sergey Igorievich et al. Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma. In: Nature genetics, 2012, vol. 44, n° 2, p. 133-9. doi: 10.1038/ng.1026 https://archive-ouverte.unige.ch/unige:34654

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Deposited on : 2014-03-07

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