%0 Journal Article
%T Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype
%A George Calin
%A Guglielmina N Ranzani
%A Dino Amadori
%A Vlad Herlea
%A Irina Matei
%A Giuseppe Barbanti-Brodano
%A Massimo Negrini
%J BMC Genetics
%D 2001
%I BioMed Central
%R 10.1186/1471-2156-2-14
%X We analyzed 50 gastric carcinomas (GCs) for mutations in the BLM poly(A) tract aswell as in the coding microsatellites of the TGF¦Â1-RII, IGFIIR, hMSH3, hMSH6, BAX, WRN, RECQL and CBL genes.BLM mutations were found in 27% of MMP+ GCs (4/15 cases) but not in any of the MMP negative GCs (0/35 cases). The frequency of mutations in the other eight coding regions microsatellite was the following: TGF¦Â1-RII (60 %), BAX (27%), hMSH6 (20%),hMSH3 (13%), CBL (13%), IGFIIR (7%), RECQL (0%) and WRN (0%). Mutations in BLM appear to be more frequently associated with frameshifts in BAX and in hMSH6and/or hMSH3. Tumors with BLM alterations present a higher frequency of unstable mono- and trinucleotide repeats located in coding regions as compared with mutator phenotype tumors without BLM frameshifts.BLM frameshifts are frequent alterations in GCs specifically associated with MMP+tumors. We suggest that BLM loss of function by MSI may increase the genetic instability of a pre-existent unstable genotype in gastric tumors.Cancer is a progressive genetic disease characterized by progressive accumulation of mutations in both coding and non-coding sequences [1]. Simple sequence repeats or microsatellites are highly unstable in some human neoplasms, identifying a class of tumors with the microsatellite mutator phenotype (MMP+) (for review see [2]). MMP+ve status is defined by instability in more than 30% of analised microsatellites, including at least one mononucleotide (such as BAT26 or BAT25) [3]. Microsatellite instability (MSI) has been described as a frequent genetic alteration in various human solid tumors including sporadic and familial gastric carcinomas (GCs). In almost all patients with hereditary nonpolyposis colorectal cancer (HNPCC), molecular studies have shown that MSI is caused by germline mutations in genes encoding proteins required for DNA mismatch repair (MMR) [4]. Genes such as hMSH2, hMLH1, PMS1, PMS2 and hMSH6/GTBP[5-8], were defined as "caretakers" because, when di
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