Evidence of a possible epigenetic inactivation mechanism operating on a region of mouse chromosome 19 in gamma-radiation-induced thymic lymphomas.
Loss of heterozygosity (LOH) analysis, performed in 68 gamma-radiation-induced primary thymic lymphomas of F1 hybrid mice, provided evidence of significant LOH on chromosome 19 in a region defined by the D19Mit106 (22 cM) and D19Mit100 (27 cM) markers (Thymic Lymphoma Suppressor Region 8, TLSR8). Cd95 and Pten, two genes mapped at this region, were inactivated in a vast majority of these tumors (85.3% for Cd95 and 61.8% for Pten). Moreover, altered expression of Cd95 and Pten occurred concomitantly in 34 of 68 (50%) thymic lymphomas suggesting a coordinated mechanism of inactivation of these genes. Surprisingly, we also found that Jak2, a proto-oncogene located between Cd95 and Pten, was simultaneously inactivated in a significant fraction of the tumors analysed (24 of 34, 70.6%). Taken together these findings and the lack of mutations in the coding sequences of the mentioned genes clearly suggest a possible regional epigenetic inactivation mechanism on mouse chromosome 19 operating during the development of these tumors.
Santos
J
J
Departmento de Biología, Laboratorio de Genética Molecular Humana, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049-Madrid, Spain.
Herranz
M
M
Fernández
M
M
Vaquero
C
C
López
P
P
Fernández-Piqueras
J
J
D000818:Animals; D002875:Chromosomes / Q000235:genetics / Q000528:radiation effects; D003433:Crosses, Genetic; D005720:Gamma Rays / Q000009:adverse effects; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D053614:Janus Kinase 2; D019656:Loss of Heterozygosity; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins; D013953:Thymus Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D019014:fas Receptor / Q000235:genetics
D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D019014:fas Receptor; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase