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

Détails

ID Serval
serval:BIB_6F3F7F30A59D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma.
Périodique
Nature Genetics
Auteur(s)
Nikolaev S.I., Rimoldi D., Iseli C., Valsesia A., Robyr D., Gehrig C., Harshman K., Guipponi M., Bukach O., Zoete V., Michielin O., Muehlethaler K., Speiser D., Beckmann J.S., Xenarios I., Halazonetis T.D., Jongeneel C.V., Stevenson B.J., Antonarakis S.E.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Statut éditorial
Publié
Date de publication
2012
Volume
44
Numéro
2
Pages
133-139
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
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.
Mots-clé
Base Sequence, Cadherins/genetics, Cell Line, Tumor, Cohort Studies, DNA Repair/genetics, Desmocollins, Exome/genetics, Humans, MAP Kinase Kinase 1/antagonists & inhibitors, MAP Kinase Kinase 1/genetics, MAP Kinase Kinase 2/antagonists & inhibitors, MAP Kinase Kinase 2/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
Pubmed
Web of science
Création de la notice
12/01/2012 16:04
Dernière modification de la notice
20/08/2019 14:28
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