Tumour suppressor genes at chromosome 3 and cancer pathogenesis

Research output: Contribution to conferenceAbstract

Abstract

The short arm of chromosome 3 is frequently altered in human cancer of different tissue origin. Certain regions on chromosome arm 3p are defined by frequent hemi- and homozygous deletions in various tumorigenic cell lines and carcinoma tissues. Also, regions at 3p have been defined by elimination in microcell hybrids parallel to increased tumourigenecity in SCID mice. We have analysed chromosome instability and several genes involved in tumour pathogenesis at 3p, such as: VHL (angiogenesis), RIITGFB (antigrowth control), CATNB (cell adhesion and transcriptional control), MLH1 (mismatch repair) and FHIT (apoptosis). 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 that have germ line mutation in the BRCA2 gene. The instability of genes and chromosome regions in BRCA2 tumours partly overlap with fragile sites in the human genome. The chromosome instability in BRCA2 tumours reflects the DNA repair mechanism of the gene product. By studying eleven tumour types we have shown that the importance of C3CER1 (chromosome 3 common eliminated region 1) transgresses tissue specificity. Comparative studies on losses of VHL, FHIT/FRA3B and C3CER1 show that the C3CER1 region is preferably lost in human tumours. Alterations in RIITGFB, CATNB and MLH1 are of interest in relation to several malignancies, particularly those of gastrointestinal origin. By analysing the effect of mismatch repair deficiency on tumourigenesis we have shown that microsatellite instability affects genes containing short repeated sequences, including the RIITGFB gene. We conclude that some of our results reflect a synergism of TSG loss at the chromosome 3p region in relation to the biological behaviour of tumour cells and tumour pathogenesis.
Original languageIcelandic
Pages231-231
Number of pages1
Publication statusPublished - 25 Apr 2005
Event2005 World DNA and Genome Day - Dalian, Dalian, China
Duration: 25 Apr 200529 Apr 2005

Conference

Conference2005 World DNA and Genome Day
Country/TerritoryChina
CityDalian
Period25/04/0529/04/05

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