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Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype

George Calin12, Guglielmina N Ranzani3, Dino Amadori4, Vlad Herlea5, Irina Matei6, Giuseppe Barbanti-Brodano1 and Massimo Negrini1*

Author Affiliations

1 Department of Experimental and Diagnostic Medicine, Section of Microbiology, University of Ferrara, Via Luigi Borsari 46, 44100 Ferrara, Italy

2 Kimmel Cancer Center, Section of Immunology and Microbiology, Philadelphia PA 19107, USA

3 Department of Genetics and Microbiology, University of Pavia, 27100 Pavia, Italy

4 Morgagni-Pierantoni Hospital and Istituto Oncologico Romagnolo, 47100 Forli, Italy

5 Department of Pathology, Fundeni Hospital, 72437 Bucharest, Romania

6 University of Bucharest, Section of Biology, 72297 Bucharest, Romania and Program in Developmental Biology, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 1X8, Canada

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BMC Genetics 2001, 2:14  doi:10.1186/1471-2156-2-14

Published: 14 August 2001



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).


We analyzed 50 gastric carcinomas (GCs) for mutations in the BLM poly(A) tract aswell as in the coding microsatellites of the TGFβ1-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: TGFβ1-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.