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




Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Genetics

, 2:14

First Online: 14 August 2001Received: 19 May 2001Accepted: 14 August 2001

Abstract

BackgroundGenomic 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.

MethodsWe analyzed 50 gastric carcinomas GCs for mutations in the BLM polyA tract aswell as in the coding microsatellites of the TGFβ1-RII, IGFIIR, hMSH3, hMSH6, BAX, WRN, RECQL and CBL genes.

ResultsBLM 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 hMSH6 and-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.

ConclusionsBLM 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2156-2-14 contains supplementary material, which is available to authorized users.

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Autor: George Calin - Guglielmina N Ranzani - Dino Amadori - Vlad Herlea - Irina Matei - Giuseppe Barbanti-Brodano - Massimo Negr

Fuente: https://link.springer.com/article/10.1186/1471-2156-2-14







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