

![]() |
Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma |
|
Authors | ![]() | |
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 Sequence — Cadherins/genetics — Cell Line, Tumor — Cohort Studies — DNA Repair/genetics — Desmocollins — Exome/genetics — Humans — MAP Kinase Kinase 1/antagonists & inhibitors/genetics — MAP Kinase Kinase 2/antagonists & inhibitors/genetics — Melanoma/genetics — Mitogen-Activated Protein Kinase 1/genetics — Molecular Sequence Data — Mutation — Proto-Oncogene Proteins B-raf/genetics — Receptors, LDL/genetics — Skin Neoplasms/genetics — Tumor Suppressor Proteins/genetics — Ultraviolet Rays/adverse effects | |
Identifiers | DOI: 10.1038/ng.1026 PMID: 22197931 | |
Full text | ||
Structures | ||
Research group | Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248) | |
Citation (ISO format) | 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 |