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


Autoria(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.
Data(s)

2012

Resumo

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.

Identificador

http://serval.unil.ch/?id=serval:BIB_6F3F7F30A59D

isbn:1546-1718 (Electronic)

pmid:22197931

doi:10.1038/ng.1026

isiid:000299664400009

Idioma(s)

en

Fonte

Nature Genetics, vol. 44, no. 2, pp. 133-139

Palavras-Chave #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
Tipo

info:eu-repo/semantics/article

article