title: Somatic MMR gene mutations as a cause for MSI-H sebaceous neoplasms in Muir-Torre syndrome-like patients.
abstract: 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.
authors.affiliation: Edouard Herriot hospital, Central Service of Pathology, Tumor Biology Laboratory, Lyon, France.
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Joly
authors.forename: Valéry
authors.initials: V
authors.lastname: Attignon
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Saurin
authors.forename: Françoise
authors.initials: F
authors.lastname: Desseigne
authors.forename: Dominique
authors.initials: D
authors.lastname: Leroux
authors.forename: Tanguy
authors.initials: T
authors.lastname: Martin-Denavit
authors.forename: Sophie
authors.initials: S
authors.lastname: Giraud
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Bonnet-Dupeyron
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Jessie
authors.initials: J
authors.lastname: Auclair
authors.forename: Chloé
authors.initials: C
authors.lastname: Grand-Masson
authors.forename: Carole
authors.initials: C
authors.lastname: Audoynaud
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
mesh_terms: D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D055653:Muir-Torre Syndrome / Q000235:genetics*; D009154:Mutation; D012626:Sebaceous Gland Neoplasms / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D004268:DNA-Binding Proteins
keywords: Lynch syndrome; MLH1; MSH2; MSH6; MSI-H tumors; Muir-Torre syndrome; PMS2