Tumor Suppressor Genes on Human Chromosome 3 and Cancer Pathogenesis

Cancer Genomics - Proteomics

SIGURDUR INGVARSSON¹ 

[1] Institute for Experimental Pathology, University of Iceland at Keldur, 112-Reykjavik, Iceland Institute for Experimental Pathology, University of Iceland at Keldur, 112-Reykjavik, Iceland Institute for Experimental Pathology, University of Iceland at Keldur, 112-Reykjavik, Iceland

关键词: Tumor suppressor gene;    chromosome 3;    FHIT;    chromosome instability;    mutation;    FRA3B;    VHL;    CER1;    elimination test;    review;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

The short arm of chromosome 3 is frequently altered in human cancers of different tissue origin. Certain regions on the chromosome arm 3p have been defined by deletion studies in human cancer cells and tissues. Also, regions at 3p are eliminated in microcell hybrids parallel to increased tumorigenicity in immunosuppressed mice. We have analysed chromosome instability and several genes involved in tumor pathogenesis at 3p, such as VHL, RIITGFB, CATNB, MLH1 and FHIT. By studying eleven tumor types, we have shown that the importance of CER1 (common eliminated region 1) transgresses tissue specificity. Comparative studies on losses of VHL, FHIT/FRA3B and CER1 show that the CER1 region is preferably lost in human tumors. Alterations of FHIT are associated with reduced survival of breast and colon cancer patients. The FHIT gene is located at the constitutive fragile region, FRA3B. Chromosome 3, particularly FHIT, is unstable in breast cancer patients who have germ line mutation in the BRCA2 gene. The chromosome instability in BRCA2 tumors reflects the DNA repair mechanism of the gene product Brca2. It can be concluded that our results reflect a synergism of tumor suppressor gene (TSG) losses at the chromosome 3p region in relation to the biological behavior of tumor cells and tumor pathogenesis.

【 授权许可】

Unknown