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Published on: January 7, 2019
Allelic loss analysis of lymphomas induced in Fas-heterozygous deficient mice
Shoji Ogawa1, Doo-Pyo Hong, Nobuko Mori
1Department of Veterinary Sciences, College of Agriculture, Osaka Prefecture University, 102 Gakuen-cho, Sakai, Osaka 599-8570, Japan.
Abstract:
Mutations of Fas (CD95/Apo-1) gene have been reported in various malignancies and therefore the Fas gene has been considered to be a tumor suppressor gene. To examine an involvement of Fas gene as a tumor suppressor gene in radiation lymphomagenesis, we examined the loss of heterozygosity (LOH) in lymphomas from (MSM/Ms x MRL-MpJ/Fas (lpr)) F(1) and (BALB/cHeA x MRL-MpJ/Fas (lpr)) F(1) hybrid mice. Lymphoma development by X-irradiation was efficiently observed in both F(1) hybrids. Frequent LOH was found on chromosomes 12 and 4 in the tumors from both F(1) mice, but no allelic loss on chromosome 19 containing Fas locus was found, and no wild-type allele of the Fas gene was lost in 51 lymphomas. Therefore, the putative tumor-suppressor gene regions responsible for lymphomagenesis might not considerably differ due to the Fas gene status.
Insights
The Fas gene, considered a tumor suppressor, was investigated in radiation-induced lymphomas. Researchers found no evidence of Fas gene loss, suggesting other genetic regions are key in lymphomagenesis.
Area of Science:
- Oncology
- Genetics
- Immunology
Background:
- The Fas gene (CD95/Apo-1) is implicated in various cancers and functions as a tumor suppressor.
- Radiation exposure can induce lymphomagenesis, a process potentially involving tumor suppressor genes.
Purpose of the Study:
- To investigate the role of the Fas gene as a tumor suppressor in radiation-induced lymphomagenesis.
- To analyze loss of heterozygosity (LOH) at the Fas locus in radiation-induced lymphomas.
Main Methods:
- Utilized (MSM/Ms x MRL-MpJ/Fas (lpr)) F(1) and (BALB/cHeA x MRL-MpJ/Fas (lpr)) F(1) hybrid mice.
- Induced lymphoma development using X-irradiation.
- Examined loss of heterozygosity (LOH) on chromosomes 12, 4, and 19 (containing the Fas locus) in lymphoma tissues.
Main Results:
- Lymphoma development was efficiently observed in both F(1) hybrid mouse models following X-irradiation.
- Frequent LOH was detected on chromosomes 12 and 4 in the developed tumors.
- No allelic loss was observed at the Fas locus on chromosome 19.
- The wild-type allele of the Fas gene was not lost in any of the 51 analyzed lymphomas.
Conclusions:
- The Fas gene status does not appear to significantly influence the location of critical tumor-suppressor gene regions involved in radiation-induced lymphomagenesis.
- Other chromosomal regions, such as chromosomes 12 and 4, harbor key genetic alterations in this model of lymphomagenesis.

