title: Molecular screening in Sicilian families with hereditary non-poliposis colorectal cancer (H.N.P.C.C.) syndrome: identification of a novel mutation in MSH2 gene.
abstract: HNPCC is an autosomal inherited cancer syndrome characterized by germinal and somatic mutations of DNA mismatch repair (MMR) genes. The inherited mutation in one allele together with an acquired defect in the other allele of an MMR gene leads to accelerate tumor progression. In this study we analyzed a cohort of 11 subjects belonging to four Sicilian families with HNPCC suspected by molecular analysis of coding regions of hMSH2 (NC_000002) and hMLH1 (NC_000003) genes. Molecular analysis has detected the presence of two mutations in gene MSH2 and one mutation in MHL1 gene. In addition, we found a novel mutation consisting in a G deletion at 914 codon of the exon 16 in the MSH2 gene. This deletion leads to a stop codon due to a frame-shift, resulting in a truncated protein. We extended genetic analysis to the other family members and the same mutation was detected in three sisters and in one of the two healthy daughters. This mutation is correlated with clinical findings revealed in genealogic tree and it represents a novel mutation responsible of HNPCC.
authors.affiliation: Dep. of Surgery, University of Catania, Italy. Electronic address: andreacavallaro@tiscali.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavallaro
authors.affiliation: Dep. of Biomedical Sciences, University of Catania, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Russo
authors.affiliation: Dep. of Surgical Science, Organ Transplantation and Advanced Technology, University of Catania, Italy. Electronic address: vito.catania@policlinico.unict.it.
authors.forename: Vito Emanuele
authors.initials: VE
authors.lastname: Catania
authors.affiliation: Dep. of Biomedical Sciences, University of Catania, Italy.
authors.forename: Bartolomea
authors.initials: B
authors.lastname: Ficili
authors.affiliation: Hospital Umberto I, Oncology Department, Siracusa, Italy. Electronic address: oncologia@raosr.it.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Romano
authors.affiliation: Dep. of Surgical Science, Organ Transplantation and Advanced Technology, University of Catania, Italy. Electronic address: andrewfailla@yahoo.it.
authors.forename: Andrea Valentino
authors.initials: AV
authors.lastname: Failla
authors.affiliation: Dep. of Surgery, University of Catania, Italy. Electronic address: alecap@unict.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cappellani
authors.affiliation: Dep. of Surgical Science, Organ Transplantation and Advanced Technology, University of Catania, Italy. Electronic address: cammisul@unict.it.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Cammisuli
authors.affiliation: Dep. of Biomedical Sciences, University of Catania, Italy. Electronic address: mviola@unict.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Viola
authors.affiliation: Dep. of Biomedical Sciences, University of Sassari, Italy. Electronic address: rmadeddu@uniss.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Madeddu
authors.affiliation: Department of Clinical and Experimental Medicine, Policlinico "G. Martino", University of Messina, Italy. Electronic address: vtrichilo@unime.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Trichilo
authors.affiliation: Dep. of Biomedical Sciences, University of Catania, Italy. Electronic address: mlibra@unict.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Libra
authors.affiliation: Dep. of Biomedical Sciences, University of Catania, Italy. Electronic address: stravali@unict.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Travali
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D012802:Sicily; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: Colorectal cancer; HNPCC; MMR genes; Molecular analysis