Journal Article

Loss of <i>Blm</i> enhances basal cell carcinoma and rhabdomyosarcoma tumorigenesis in <i>Ptch1<sup>+/−</sup></i> mice

Parastoo Davari, Jennifer L. Hebert, Donna G. Albertson, Bing Huey, Ritu Roy, Maria L. Mancianti, Andrew E. Horvai, Lisa D. McDaniel, Roger A. Schultz and Ervin H. Epstein

in Carcinogenesis

Volume 31, issue 6, pages 968-973
Published in print June 2010 | ISSN: 0143-3334
Published online December 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp309
Loss of Blm enhances basal cell carcinoma and rhabdomyosarcoma tumorigenesis in Ptch1+/− mice

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Basal cell carcinomas (BCCs) have relative genomic stability and relatively benign clinical behavior but whether these two are related causally is unknown. To investigate the effects of introducing genomic instability into murine BCCs, we have compared ionizing radiation-induced tumorigenesis in Ptch1+/− mice versus that in Ptch1+/− mice carrying mutant Blm alleles. We found that BCCs in Ptch1+/− Blmtm3Brd/tm3Brd mice had a trend toward greater genomic instability as measured by array comprehensive genomic hybridization and that these mice developed significantly more microscopic BCCs than did Ptch1+/− Blm+/tm3Brd or Ptch1+/− Blm+/+ mice. The mutant Blm alleles also markedly enhanced the formation of rhabdomyosarcomas (RMSs), another cancer to which Ptch1+/ mice and PTCH1+/ (basal cell nevus syndrome) patients are susceptible. Highly recurrent but different copy number changes were associated with the two tumor types and included losses of chromosomes 4 and 10 in all BCCs and gain of chromosome 10 in 80% of RMSs. Loss of chromosome 11 and 13, including the Trp53 and Ptch1 loci, respectively, occurred frequently in BCCs, suggesting tissue-specific selection for genes or pathways that collaborate with Ptch deficiency in tumorigenesis. Despite the quantitative differences, there was no dramatic qualititative difference in the BCC or RMS tumors associated with the mutant Blm genotype.

Journal Article.  3440 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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