Loss of heterozygosity at the proximal-mid part of mouse chromosome 4 defines two novel tumor suppressor gene loci in T-cell lymphomas.
Recent studies in our laboratory reported frequent loss of heterozygosity (LOH) on mouse chromosome 4 in T-cell lymphomas, identifying three candidate tumor suppressor regions (TLSR1-3). To determine the possible existence of other tumor suppressor gene loci on the proximal-mid part of chromosome 4 and to clarify whether the p16(INK4a) (alpha and beta) and p15(INK4b) genes are the inactivation targets of deletion at TLSR1, we have tested 73 gamma-radiation-induced T-cell lymphomas of F1 hybrid mice by LOH analysis. Frequent LOH was found at the INK4a and INK4b loci and the surrounding markers D4Mit77, D4Mit245 and D4Wsm1. In addition, we identified two distinct regions of significant allelic losses in the proximal-mid part of chromosome 4, defined by the markers D4Mit116 (TLSR4) and D4Mit21 (TLSR5). Taken together, this evidence and our previous data indicate the existence of at least five different candidate sites for tumor suppressor genes on chromosome 4, thus revealing a main role for this chromosome in the development of mouse T-cell lymphomas.
Meléndez
B
B
Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Spain.
Santos
J
J
Fernández-Piqueras
J
J
D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005720:Gamma Rays / Q000009:adverse effects; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D005820:Genetic Testing; D019656:Loss of Heterozygosity; D016399:Lymphoma, T-Cell / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D051379:Mice / Q000235:genetics*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; C493968:Cdkn2b protein, mouse; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins