Professional article

Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma

Published inNature genetics, vol. 44, no. 2, p. 133-139
Publication date2012

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.

  • 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
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. 133–139. doi: 10.1038/ng.1026
Main files (1)
Article (Published version)
ISSN of the journal1061-4036

Technical informations

Creation02/14/2014 5:54:00 PM
First validation02/14/2014 5:54:00 PM
Update time03/14/2023 9:00:36 PM
Status update03/14/2023 9:00:36 PM
Last indexation08/29/2023 10:36:54 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack