Somatic MMR gene mutations as a cause for MSI-H sebaceous neoplasms in Muir-Torre syndrome-like patients.
Fiche publication
Date publication
mars 2015
Journal
Human mutation
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence
Tous les auteurs :
Joly MO, Attignon V, Saurin JC, Desseigne F, Leroux D, Martin-Denavit T, Giraud S, Bonnet-Dupeyron MN, Faivre L, Auclair J, Grand-Masson C, Audoynaud C, Wang Q
Lien Pubmed
Résumé
Sebaceous neoplasms are a major clinical feature of Muir-Torre syndrome (MTS) associated with visceral malignancies, especially colorectal and endometrial tumors. The diagnosis of MTS relies largely on the microsatellite instability (MSI) phenotype in tumors, suggesting germline mutations in DNA mismatch repair (MMR) genes responsible for the inherited disease. We hypothesized that in some MSI-H sebaceous tumors, acquired rather than inherited mutations in MMR genes could be involved. Using next-generation sequencing, we screened MMR gene mutations in 18 MSI-H sebaceous tumors. We found mutations in 17 samples (94%). Indeed, 12/17 (71%) were shown to carry acquired somatic mutations and among 12 samples, seven were shown to be associated with additional somatic alterations like loss of heterozygosity or multiple mutations, suggesting somatic second hits. Our findings strongly suggest that somatic MMR deficiency is responsible for a proportion of MSI-H sebaceous tumors.
Mots clés
DNA Mismatch Repair, DNA-Binding Proteins, genetics, High-Throughput Nucleotide Sequencing, Humans, Muir-Torre Syndrome, genetics, Mutation, Sebaceous Gland Neoplasms, genetics, Sequence Analysis, DNA
Référence
Hum. Mutat.. 2015 Mar;36(3):292-5