| Germline MLH1 and MSH2 mutations in Italian pancreatic cancer patients with suspected Lynch syndrome. | |
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MedLine Citation:
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PMID: 19728162 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lynch syndrome is an inherited cancer syndrome caused by germline mutations in mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. LS predisposes to high risk of early-onset colorectal, endometrial and other tumors. Patients with Lynch syndrome have also been shown to have an elevated risk for pancreatic cancer (PC). In this study, we aimed to estimate the frequency of suspected Lynch syndrome among a series of 135 PC patients. Further, we wanted to determine the frequency of MMR gene mutations in the suspected Lynch syndrome cases. We also aimed to verify the pathogenicity of any novel non-truncating variants we might detect with a functional assay. Based on personal and/or familial cancer history, 19 patients were classified as suspected Lynch syndrome cases. DNA material for mutation analysis was available for eleven of them. Four patients were found to carry a total of five MLH1 or MSH2 variants. Of these, MSH2-Q402X, MSH2-G322D, and MLH1-K618A had been previously reported, while the MSH2-E205Q and MSH2-V367I variants were novel. MSH2-Q402X is a known stop mutation and reported here for the first time here in association with PC. MLH1-K618A was found in the unaffected branch of a kindred, suggesting that it may be a polymorphism or a low penetrance variant. MSH2-G322D likely does not cause a MMR defect, although this variant has also been associated with breast cancer as indeed seen in our patient. The novel variants MSH2-E205Q and MSH2-V367I were found in the same patient. Both novel variants were however functional in the applied MMR assay. Our findings suggest that only a small subset of pancreatic cancer patients carry pathogenic MMR mutations. |
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Authors:
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S Gargiulo; M Torrini; S Ollila; S Nasti; L Pastorino; R Cusano; L Bonelli; L Battistuzzi; L Mastracci; W Bruno; V Savarino; S Sciallero; G Borgonovo; M Nyström; G Bianchi-Scarrà; C Mareni; P Ghiorzo |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Familial cancer Volume: 8 ISSN: 1573-7292 ISO Abbreviation: Fam. Cancer Publication Date: 2009 |
Date Detail:
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Created Date: 2009-11-04 Completed Date: 2010-01-08 Revised Date: 2011-11-24 |
Medline Journal Info:
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Nlm Unique ID: 100898211 Medline TA: Fam Cancer Country: Netherlands |
Other Details:
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Languages: eng Pagination: 547-53 Citation Subset: IM |
Affiliation:
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Department of Oncology, Biology and Genetics, University of Genoa, 16132 Genoa, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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genetics* Adult Base Sequence Colorectal Neoplasms, Hereditary Nonpolyposis / complications, genetics* DNA Mismatch Repair / genetics DNA Mutational Analysis Female Genetic Predisposition to Disease* Germ-Line Mutation Humans Immunohistochemistry Italy Male Microsatellite Instability Middle Aged MutS Homolog 2 Protein / genetics* Nuclear Proteins / genetics* Pancreatic Neoplasms / genetics* Pedigree Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
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GTB07001//Telethon |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/MLH1 protein, human; 0/Nuclear Proteins; EC 3.6.1.3/MSH2 protein, human; EC 3.6.1.3/MutS Homolog 2 Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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