Genomic alterations of 332 malignant lymphoma using BAC array CGH analysis. Homo sapiens

Clonal heterogeneity in lymphoid malignancies has been recently reported in adult T-Cell lymphoma/leukemia, peripheral T-cell lymphoma, not otherwise specified, and mantle cell lymphoma (MCL). Our analysis was extended to other types of lymphoma including marginal zone lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL). We examined the results of array comparative genomic hybridization analysis for 332 cases to determine if clonal heterogeneity existed in each case. Results showed that frequencies of clonal heterogeneity varied from 25% to 69% among different types of lymphoma. Multivariate analysis indicated that MCL and DLBCL with clonal heterogeneity showed a significantly poorer prognosis. Interestingly, 9p21.3 (CDKN2A/ 2B) loss and 17p13 (TP53, ATP1B2, SAT2, SHBG) loss were common regions among various types of lymphoma with clonal heterogeneity, suggesting at least in part that loss of these genes may play a role in clonal heterogeneity. Overall design: We analyzed previously untreated 332 cases of lymphoma (comprising 29 cases of mantle cell lymphoma, 117 cases of diffuse large B-cell lymphoma (DLBCL), 79 cases of Follicular lymphoma, 24 cases of Burkitt lymphoma, 31 cases of mucosa-associated lymphoid tissue (MALT) lymphoma, and 51 peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)).

淋巴恶性肿瘤中的克隆异质性（clonal heterogeneity）近期已有报道，涉及成人T细胞淋巴瘤/白血病、外周T细胞淋巴瘤-非特指型以及套细胞淋巴瘤（MCL）。本研究将分析范围拓展至其他淋巴瘤类型，包括边缘区淋巴瘤、滤泡性淋巴瘤以及弥漫大B细胞淋巴瘤（DLBCL）。我们对332例样本的阵列比较基因组杂交（array comparative genomic hybridization）分析结果进行了检测，以明确每例样本是否存在克隆异质性。结果显示，不同淋巴瘤类型的克隆异质性发生率在25%至69%之间波动。多元分析表明，携带克隆异质性的套细胞淋巴瘤（MCL）与弥漫大B细胞淋巴瘤（DLBCL）患者的预后显著更差。值得注意的是，在存在克隆异质性的各类淋巴瘤中，9p21.3（CDKN2A/2B）缺失与17p13（TP53、ATP1B2、SAT2、SHBG）缺失均为常见的染色体区域异常，这提示这些基因的缺失至少在一定程度上参与了克隆异质性的发生。总体研究设计：本研究分析了332例既往未接受治疗的淋巴瘤病例，其中包括29例套细胞淋巴瘤、117例弥漫大B细胞淋巴瘤（DLBCL）、79例滤泡性淋巴瘤、24例伯基特淋巴瘤、31例黏膜相关淋巴组织（MALT）淋巴瘤以及51例外周T细胞淋巴瘤-非特指型（PTCL-NOS）。