title: Synchronous gastric and sebaceous cancers, a rare manifestation of MLH1-related Muir-Torre syndrome.
abstract: Muir-Torre syndrome (MTS), a rare variant of the hereditary non polyposis colorectal cancer syndrome, is an autosomal dominant genodermatosis characterised by coincidence of sebaceous gland neoplasms (sebaceous adenoma, epithelioma, or carcinoma) and at least one internal malignancy. The underlying cause of MTS is a germline mutation in DNA mismatch repair genes MSH2, MLH1 and MSH6. We report the case of a 52-year-old caucasian woman with the development of metachronous colon cancer at the age of 38 years, uterine cancer at the age of 43 years, and unique occurrence of synchronous gastric and sebaceous carcinomas related to germline point mutation c. 2194A>T in the last exon of MLH1 gene, resulting in truncated protein in C-terminal region p. Lys732X due to premature stop codon. This mutation, not previously reported in MTS, disrupts the function of MutL complexes presumably by preventing the interaction with PMS1/PMS2 and impairing the endonuclease active site. This case points out the importance of sebaceous neoplasia, especially sebaceous adenocarcinoma, as cutaneous markers of MTS for timely implementation of cancer screening programs.
authors.affiliation: 2nd Department of Internal Medicine, 3rd Faculty of Medicine, Charles University Prague ; Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic Prague.
authors.forename: Jiří
authors.initials: J
authors.lastname: Svec
authors.affiliation: Institute of Biology and Medical Genetics, 1st Faculty of Medicine and General Teaching Hospital, Charles University Prague.
authors.forename: Lucie
authors.initials: L
authors.lastname: Schwarzová
authors.affiliation: Institute of Biology and Medical Genetics, 1st Faculty of Medicine and General Teaching Hospital, Charles University Prague.
authors.forename: Bohumila
authors.initials: B
authors.lastname: Janošíková
authors.affiliation: Institute of Biology and Medical Genetics, 1st Faculty of Medicine and General Teaching Hospital, Charles University Prague.
authors.forename: Jitka
authors.initials: J
authors.lastname: Stekrová
authors.affiliation: Department of Pathology, 3rd Faculty of Medicine, Charles University Prague.
authors.forename: Václav
authors.initials: V
authors.lastname: Mandys
authors.affiliation: 2nd Department of Internal Medicine, 3rd Faculty of Medicine, Charles University Prague.
authors.forename: Milan
authors.initials: M
authors.lastname: Kment
authors.affiliation: Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic Prague.
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodička
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D018266:Adenocarcinoma, Sebaceous / Q000235:genetics* / Q000473:pathology; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D055653:Muir-Torre Syndrome / Q000235:genetics* / Q000473:pathology; D000070957:MutL Protein Homolog 1; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D017354:Point Mutation; D012626:Sebaceous Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1
keywords: MLH1; Muir-Torre syndrome; gastric cancer; germline mutation; sebaceous adenocarcinoma