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FHIT alterations in breast cancer
1Institute for Experimental Pathology, University of Iceland, Reykjavik, Iceland.
Abstract:
The FHIT gene encodes a diadenosine hydrolase and may be involved in growth control pathways of the cell. Studies on protein-protein interactions, cell lines, including tumourigenicity tests, and knockout mice suggest that the Fhit protein is involved in cell proliferation and apoptosis, and might act as a tumour suppressor. In several different cancers, including breast cancer, alterations in the FHIT gene have been detected in high frequency. The most common alterations are: deletions, DNA hypermethylation, abnormal transcripts and reduced expression at RNA and protein level. The FHIT gene is located at the FRA 3B fragile site at chromosome 3p 14.2, and alterations in the FHIT gene and Fhit protein have been found associated with genome instability, particularly in BRCA 2 mutated breast tumours. This paper will focus on some of the functional aspects of the Fhit protein with respect to tumour pathogenesis and on aberrations detected in breast cancer.
Insights
The FHIT gene, a potential tumor suppressor, shows frequent alterations in breast cancer, including deletions and reduced expression. These changes may contribute to tumor development and genome instability.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- The FHIT gene encodes a diadenosine hydrolase implicated in cellular growth control.
- The Fhit protein is suggested to function as a tumor suppressor, influencing cell proliferation and apoptosis.
- Alterations in the FHIT gene are frequently observed in various cancers, notably breast cancer.
Purpose of the Study:
- To investigate the functional roles of the Fhit protein in tumor pathogenesis.
- To detail the specific aberrations of the FHIT gene and Fhit protein in breast cancer.
Main Methods:
- Analysis of protein-protein interactions.
- Studies on cell lines, including tumorogenicity tests.
- Examination of knockout mouse models.
- Detection of gene alterations such as deletions, hypermethylation, and changes in RNA/protein expression.
Main Results:
- Evidence suggests Fhit protein's involvement in cell proliferation and apoptosis, supporting its tumor suppressor role.
- Common FHIT gene alterations in breast cancer include deletions, DNA hypermethylation, abnormal transcripts, and reduced expression.
- FHIT gene alterations are linked to genome instability, particularly in BRCA2-mutated breast tumors.
Conclusions:
- The FHIT gene and Fhit protein play a significant role in tumor suppression.
- Aberrations in FHIT are prevalent in breast cancer and associated with genomic instability.
- Understanding FHIT's function is crucial for comprehending breast cancer pathogenesis.