title: Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype.
abstract: BACKGROUND
  Genomic instability has been reported at microsatellite tracts in few coding sequences. We have shown that the Bloom syndrome BLM gene may be a target of microsatelliteinstability (MSI) in a short poly-adenine repeat located in its coding region. To further characterize the involvement of BLM in tumorigenesis, we have investigated mutations in nine genes containing coding microsatellites in microsatellite mutator phenotype (MMP) positive and negative gastric carcinomas (GCs).
  
  
  METHODS
  We analyzed 50 gastric carcinomas (GCs) for mutations in the BLM poly(A) tract aswell as in the coding microsatellites of the TGFbeta1-RII, IGFIIR, hMSH3, hMSH6, BAX, WRN, RECQL and CBL genes.
  
  
  RESULTS
  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: TGFbeta1-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Experimental and Diagnostic Medicine, Section of Microbiology, University of Ferrara, Via Luigi Borsari 46, 44100 Ferrara, Italy. george.calin@mail.tju.edu
authors.forename: G
authors.initials: G
authors.lastname: Calin
authors.forename: G N
authors.initials: GN
authors.lastname: Ranzani
authors.forename: D
authors.initials: D
authors.lastname: Amadori
authors.forename: V
authors.initials: V
authors.lastname: Herlea
authors.forename: I
authors.initials: I
authors.lastname: Matei
authors.forename: G
authors.initials: G
authors.lastname: Barbanti-Brodano
authors.forename: M
authors.initials: M
authors.lastname: Negrini
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D016368:Frameshift Mutation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D018895:Microsatellite Repeats; D010641:Phenotype; D011061:Poly A / Q000235:genetics; D053484:RecQ Helicases; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics*
chemical_list: D011061:Poly A; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases