title: Molecular analysis of Fanconi anemia and mismatch repair genes in patients with colorectal carcinoma.
abstract: A cohort of 206 consecutively-collected patients with colorectal carcinoma (CRC) were screened for germline mutations in the principal DNA mismatch repair (MMR) genes, MLH1 and MSH2, and in the Fanconi anemia (FA) genes involved in homologous recombination DNA repair. Mutation analysis was performed by denaturing high-performance liquid chromatography (DHPLC) and automated sequencing. Available paraffin-embedded tumor tissues were evaluated for gene expression by immunohistochemistry. Genes of the FA pathway were found to participate in CRC pathogenesis, being silenced during disease progression and metastasis formation. Conversely, MLH1 and MSH2 genes seem to be inactivated at earlier stages of the disease. Finally, very few (about 5%) cases presented a simultaneous inactivation of the MMR and FA genes. Overall, our findings indicated that: i) mismatch DNA repair remains the main mechanism to be altered at both germline and somatic levels among CRC patients; ii) functional impairments of mismatch DNA repair and FA-related repair may represent two different pathogenetic alterations which are concurring in colorectal cancer progression.
authors.affiliation: Istituto di Chimica Biomolecolare-CNR, Sassari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Colombino
authors.forename: Antonio
authors.initials: A
authors.lastname: Avallone
authors.forename: Francesco
authors.initials: F
authors.lastname: Izzo
authors.forename: Fabiana
authors.initials: F
authors.lastname: Tatangelo
authors.forename: Mario
authors.initials: M
authors.lastname: Budroni
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.forename: Francesco
authors.initials: F
authors.lastname: Galimi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Comella
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Sini
authors.forename: Francesco
authors.initials: F
authors.lastname: Tanda
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004260:DNA Repair; D005199:Fanconi Anemia / Q000235:genetics*; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051856:Fanconi Anemia Complementation Group Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein