title: EPHA7, a new target gene for 6q deletion in T-cell lymphoblastic lymphomas.
abstract: Cryptic deletions at chromosome 6q are common cytogenetic abnormalities in T-cell lymphoblastic leukemia/lymphoma (T-LBL), but the target genes have not been formally identified. Our results build on detection of specific chromosomal losses in a mouse model of γ-radiation-induced T-LBLs and provide interesting clues for new putative susceptibility genes in a region orthologous to human 6q15-6q16.3. Among these, Epha7 emerges as a bona fide candidate tumor suppressor gene because it is inactivated in practically all the T-LBLs analyzed (100% in mouse and 95.23% in human). We provide evidence showing that Epha7 downregulation may occur, at least in part, by loss of heterozygosity (19.35% in mouse and 12.5% in human) or promoter hypermethylation (51.61% in mouse and 43.75% in human) or a combination of both mechanisms (12.90% in mouse and 6.25% in human). These results indicate that EPHA7 might be considered a new tumor suppressor gene for 6q deletions in T-LBLs. Notably, this gene is located in 6q16.1 proximal to GRIK2 and CASP8AP2, other candidate genes identified in this region. Thus, del6q seems to be a complex region where inactivation of multiple genes may cooperatively contribute to the onset of T-cell lymphomas.
authors: Departmento Biología Celular e Inmunología, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Nicolás Cabrera 1, 28049 Madrid, Spain.
authors: Pilar
authors: P
authors: López-Nieva
authors: Concepción
authors: C
authors: Vaquero
authors: Pablo
authors: P
authors: Fernández-Navarro
authors: Laura
authors: L
authors: González-Sánchez
authors: María
authors: M
authors: Villa-Morales
authors: Javier
authors: J
authors: Santos
authors: Manel
authors: M
authors: Esteller
authors: José
authors: J
authors: Fernández-Piqueras
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D002894:Chromosomes, Human, Pair 4; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000235:genetics*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D019656:Loss of Heterozygosity; D016399:Lymphoma, T-Cell / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D036141:Receptor, EphA7 / Q000235:genetics*; D018092:Kainic Acid Receptors / Q000235:genetics; D017384:Sequence Deletion; D000097806:GluK2 Kainate Receptor
chemical_list: D002135:Calcium-Binding Proteins; D036141:Receptor, EphA7; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor; C119301:Casp8ap2 protein, mouse