title: [Muir-Torre syndrome and familial colorectal cancer: 2 families with molecular genetic analysis].
abstract: BACKGROUND
  The Muir-Torre Syndrome is a rare genodermatosis, defined by the occurrence of cutaneous tumors (such as sebaceous adenomas, epitheliomas, or carcinomas, and/or keratoacanthomas), and internal malignancies. Recently, molecular analysis in hereditary non polyposis colorectal cancer demonstrated a common genetic basis, linking these two disorders, with the observation of germline mutations in the hMSH2 gene (one of the DNA mismatch repair system genes) in both syndromes. Such molecular demonstration of a single nosological entity should be clinically used to improve the indications of molecular testings in oncogenetics, still restricted to highly stringent criteria for hereditary non polyposis colorectal cancer.
  
  
  METHODS
  We identified three patients from two different families, who fulfilled the criteria for both Muir-Torre Syndrome and hereditary non polyposis colorectal cancer. The search of a germline mutation of the hMSH2 gene was performed on an affected member from each family, and their relatives with their informed consent. Within each family, all individuals with colorectal cancer were carriers of the same mutation. In the first family, this mutation was a pathogenic microinsertion, usable for predictive testing. In the second family, a missense mutation was identified, requesting further demonstration of its pathogenicity before its use in a predictive purpose.
  
  
  CONCLUSIONS
  The diagnosis of cutaneous tumors compatible with Muir-Torre syndrome should lead the dermatologist to suspect an hereditary non polyposis colorectal cancer that should bring to an oncogenetic approach: personnal and familial history of colorectal cancer, molecular analysis, recommendations for colonoscopic screening in at-risk relatives. In the case of a colorectal cancer at a young age, or in the case of familial cases, the gastroenterologist should screen for cutaneous lesions of Muir-Torre syndrome, which could add a criteria for an hereditary syndrome, and lead to molecular oncogenetic analysis.
authors.affiliation: Service de Dermatologie, Institut Gustave-Roussy, Villejuif.
authors.forename: M X
authors.initials: MX
authors.lastname: Doré
authors.forename: B
authors.initials: B
authors.lastname: Dieumegard
authors.forename: S
authors.initials: S
authors.lastname: Grandjouan
authors.forename: M F
authors.initials: MF
authors.lastname: Avril
authors.forename: C
authors.initials: C
authors.lastname: Martinet
authors.forename: M
authors.initials: M
authors.lastname: Ducreux
authors.forename: P
authors.initials: P
authors.lastname: Lasser
authors.forename: B
authors.initials: B
authors.lastname: Bressac-de Paillerets
mesh_terms: D000236:Adenoma / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D020137:Base Pair Mismatch / Q000235:genetics; D002277:Carcinoma / Q000235:genetics; D003062:Codon / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004268:DNA-Binding Proteins; D004200:Diseases in Twins / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D007636:Keratoacanthoma / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D051718:MutS Homolog 2 Protein; D016254:Mutagenesis, Insertional / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D009857:Oncogenes / Q000235:genetics; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012626:Sebaceous Gland Neoplasms / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics*; D013577:Syndrome
chemical_list: D003062:Codon; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000251:Adenosine Triphosphatases; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein