title: Microsatellite instability in colorectal-cancer patients with suspected genetic predisposition.
abstract: Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome linked to DNA-mismatch-repair (MMR) gene defects, which also account for microsatellite instability (MSI) in tumour tissues. Diagnosis is based mainly on family history, according to widely accepted criteria (Amsterdam Criteria: AC). Aim of this work was to assess MSI in colorectal-cancer patients with suspected genetic predisposition, and to verify whether MSI represents a tool to manage MMR gene (hMSH2 and hMLH1) mutation analysis. We investigated 13 microsatellites (including the 5 NCI/ICG-HNPCC markers) in 45 patients with suspected hereditary predisposition (including 16 subjects from HNPCC families fulfilling the AC). We found MSI-H (high frequency of instability, i.e., in > or =30% of the markers) in 85% of the HNPCC patients and in 16% of the non-HNPCC subjects. The 5 NCI/ICG-HNPCC microsatellites proved to be the most effective in detecting MSI, being mononucleotide repeats the most unstable markers. We investigated the association between hMSH2- and hMLH1 gene mutations and MSI. Our results indicate that AC are highly predictive both of tumour instability and of MMR-gene mutations. Therefore, as the most likely mutation carriers, HNPCC subjects might be directly analyzed for gene mutations, while to test for MSI in selected non-HNPCC patients and to further investigate MMR genes in MSI-H cases, appears to be a cost-effective way to identify subjects, other than those from kindred fulfilling AC, who might benefit from genetic testing.
authors.affiliation: Dipartimento di Genetica e Microbiologia, University of Pavia, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Calistri
authors.forename: S
authors.initials: S
authors.lastname: Presciuttini
authors.forename: G
authors.initials: G
authors.lastname: Buonsanti
authors.forename: P
authors.initials: P
authors.lastname: Radice
authors.forename: I
authors.initials: I
authors.lastname: Gazzoli
authors.forename: V
authors.initials: V
authors.lastname: Pensotti
authors.forename: P
authors.initials: P
authors.lastname: Sala
authors.forename: M
authors.initials: M
authors.lastname: Eboli
authors.forename: S
authors.initials: S
authors.lastname: Andreola
authors.forename: A
authors.initials: A
authors.lastname: Russo
authors.forename: M
authors.initials: M
authors.lastname: Pierotti
authors.forename: L
authors.initials: L
authors.lastname: Bertario
authors.forename: G N
authors.initials: GN
authors.lastname: Ranzani
mesh_terms: D000328:Adult; D020137:Base Pair Mismatch; D002648:Child; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation
chemical_list: D004273:DNA, Neoplasm