Recurrent deletions of the TNFSF7 and TNFSF9 genes in 19p13.3 in diffuse large B-cell and Burkitt lymphomas
INTERNATIONAL JOURNAL OF CANCER
Authors: Scholtysik, Rene; Nagel, Inga; Kreuz, Markus; Vater, Inga; Giefing, Maciej; Schwaenen, Carsten; Wessendorf, Swen; Truemper, Lorenz; Loeffler, Markus; Siebert, Reiner; Kueppers, Ralf
Abstract
A single nucleotide polymorphism-chip analysis of 98 cases of aggressive B-cell lymphomas revealed a recurrent deletion at 19p13 in nine of the cases. Six further cases with deletions encompassing this region were found in array-comparative genomic hybridization data of 295 aggressive B-cell lymphomas from a previous study. Three cases even showed a homozygous deletion, suggesting a tumor suppressor gene in the deleted region. Two genes encoding members of the tumor necrosis factor superfamily (TNFSF) were located in the minimally deleted region, that is, TNFSF7 and TNFSF9. As no mutations were found within the coding exons of the remaining alleles in the lymphomas with heterozygous deletions, we speculate that the deletions may mostly function through a haploinsufficiency mechanism. The cases with deletions encompassed both diffuse large B-cell lymphomas and Burkitt lymphomas, and a deletion was also found in a Hodgkin lymphoma cell line. Thus, TNFSF7 and TNFSF9 deletions are recurrent genetic lesions in multiple types of human lymphomas.
Association of CD27 and CD70 gene polymorphisms with risk of sporadic breast cancer in Chinese women in Heilongjiang Province
BREAST CANCER RESEARCH AND TREATMENT
Authors: Xu, Fengyan; Li, Dalin; Zhang, Qiujin; Fu, Zhenkun; Yuan, Weiguang; Pang, Da; Li, Dianjun
Abstract
CD27 and its ligand, CD70, are major costimulatory molecules whose interaction can regulate the expansion and differentiation of effector and memory T-cell populations. Their abnormal expression can disturb the immune response and lead to an increased risk of cancer. This study aims to evaluate the associations between single nucleotide polymorphisms (SNPs) in CD27/CD70 gene and breast cancer susceptibility. Five tagSNPs and one coding polymorphism in CD27, as well as three tagSNPs in CD70, were genotyped in a case-control study of 610 breast cancer patients and 617 healthy controls. In CD27, rs3136550 CT and rs2267966 AT genotypes were associated with a decreased risk of breast cancer (P = 0.03, OR = 0.76; P = 0.02, OR = 0.75, respectively). In CD70, AG and GG genotypes in rs1862511 and CC genotype in rs2059154 also showed significant associations with a decreased risk of breast cancer (P = 2.00 x 10(-3), OR = 0.69; P = 0.03, OR = 0.62; P = 2.00 x 10(-3), OR = 0.53; respectively). Significant associations were also found in the dominant and recessive models for rs2059154 and dominant model for rs1862511. In haplotype analysis, CCGAG haplotype in CD27 and TAA haplotype in CD70 conferred an increased risk of breast cancer (P = 5.60 x 10(-3); P = 7.75 x 10(-5), respectively), but TGC, TAC and TGA haplotypes in CD70 were associated with a decreased risk of breast cancer (P = 0.01; P = 5.2 x 10(-3); P = 2.00 x 10(-3), respectively). The associations of CCGAG, TAA, TAC and TGA haplotypes remained significant after correcting P value for multiple testing. Significant associations were shown between the SNPs of CD27 and lymph node metastasis, and ER and PR statuses. These results indicate that CD27 and CD70 gene polymorphisms may affect the risk of breast cancer and show that some SNPs are associated with breast cancer characteristics in a northern Chinese population.