Affymetrix SNP array data for recurrent deletion in 19p in DLBCLs and BLs. Homo sapiens

A single nucleotide polymorphism (SNP)-chip analysis of 98 cases of aggressive B-cell lymphomas revealed a recurrent deletion at 19p13 in 9 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 were located in the minimally deleted region, i.e. 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. Overall design: Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from whole tissue. Copy number and LOH analysis of 500K SNP/250K SNP arrays was performed on 9 cases of aggressive B-cell lymphoma harboring the described deletion. Genotyping was performed using the BRLMM-algorithm. 20 normal references (10 of those hybridized to nsp-chips) extracted from healthy blood donors, used as normals in the analysis in addition to the HapMap references provided by Affymetrix, are included in the set.

本研究对98例侵袭性B细胞淋巴瘤样本开展单核苷酸多态性（single nucleotide polymorphism, SNP）芯片分析，结果显示其中9例存在19p13区域的复发性缺失。在既往一项研究中295例侵袭性B细胞淋巴瘤的阵列比较基因组杂交（array-comparative genomic hybridization, aCGH）数据里，又发现6例存在覆盖该区域的缺失。其中3例甚至出现纯合缺失，提示该缺失区域内存在抑癌基因。
最小缺失区域内包含两个编码肿瘤坏死因子超家族成员的基因，即TNFSF7与TNFSF9。在携带杂合缺失的淋巴瘤样本中，剩余等位基因的编码外显子未检测到突变，因此我们推测此类缺失主要通过单倍体剂量不足（haploinsufficiency）机制发挥致病作用。
携带该缺失的病例既涵盖弥漫大B细胞淋巴瘤与伯基特淋巴瘤，同时在1株霍奇金淋巴瘤细胞系中也检出了该缺失。综上，TNFSF7与TNFSF9缺失是多种人类淋巴瘤中频发的遗传学异常。
实验整体设计：本研究严格按照制造商说明书，对从整块组织中提取的基因组DNA开展Affymetrix SNP芯片检测。针对9例携带上述缺失的侵袭性B细胞淋巴瘤样本，我们完成了500K SNP/250K SNP芯片的拷贝数与杂合性缺失（loss of heterozygosity, LOH）分析。基因分型采用BRLMM算法实现。本数据集纳入20份来自健康献血者的正常对照样本（其中10份与nsp芯片杂交），除Affymetrix官方提供的HapMap对照样本外，该20份样本也作为分析用正常对照纳入研究。