Lack of PMS2 gene-truncating mutations in patients with hereditary colorectal cancer.
Hereditary non-polyposis colorectal cancer (HNPCC) is a genetically heterogeneous disease for which PMS2 gene, a member of the human PMS gene family, is believed to have a marginal role. To better define the contribution of PMS2 to hereditary colorectal cancer, we investigated this gene in 22 unrelated Italian patients that, despite a positive family history and/or early onset and development of tumors with microsatellite instability (MSI), did not carry constitutional mutations of MLH1 and MSH2 genes. No mutations with clear-cut pathogenetic significance were detected in the coding regions of PMS2 gene, but only 8 polymorphisms (7 common and 1 rare, 3 silent and 5 missense) and 3 unique molecular variants (2 missense substitutions and one 3-nucleotide deletion) were seen. Lack of PMS2 truncating mutations in our study does not disagree with its supposed marginal involvement in hereditary colorectal cancer, but at the same time points out the need to investigate the phenotypic molecular and clinical characteristics more specifically associated with PMS2 mutations.
Division of Experimental Oncology 1, Centro di Riferimento Oncologico, 33081 Aviano (PN), Italy.
A
A
Viel
E
E
Novella
M
M
Genuardi
E
E
Capozzi
M
M
Fornasarig
M
M
Pedroni
M
M
Santarosa
M P
MP
De Leon
L
L
Della Puppa
M
M
Anti
M
M
Boiocchi
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases; D000328:Adult; D000368:Aged; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D045643:DNA Repair Enzymes; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005656:Fungal Proteins / Q000235:genetics; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C088996:PMS1 protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D000070956:MutL Proteins; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes