Offit K, Parsa N Z, Gaidano G, Filippa D A, Louie D, Pan D, Jhanwar S C, Dalla-Favera R, Chaganti R S
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Blood. 1993 Oct 1;82(7):2157-62.
Commonly observed in lymphoid neoplasms, deletions of 6q have been correlated with histologic and clinical subsets of non-Hodgkin's lymphoma (NHL). Our recent analysis of loss of heterozygosity of 6q loci in NHL showed two regions of minimal molecular deletion (RMD), an RMD1 at 6q25-27 and an RMD2 at 6q21-23. To establish correlations between these RMDs and regions of minimal cytogenetic deletions (RCDs) on 6q, and to define associations between RCDs and clinico-pathologic features, we have analyzed chromosome 6 abnormalities in 459 consecutively ascertained, karyotypically abnormal cases of NHL. Among these, 126 (27.5%) cases had structural abnormalities of chromosome 6, of which 94 were deletions. Analysis of these deletions identified three RCDs. An RCD1 encompassing 6q25-27 was seen in 45 intermediate-grade NHL. An RCD2 at 6q21 was observed in 11 high-grade NHL, 9 of which were of the immunoblastic subtype. An RCD3 at 6q23 was noted in 18 low-grade NHL lacking a t(14;18) translocation. Of these 18 cases, 12 were small lymphocytic NHL and, in 2 of these, del(6q) was the sole karyotypic abnormality. In 20 cases of low-grade NHL with t(14;18), the deletions spanned both RCD1 and RCD3. These data suggested the presence of at least 3 tumor suppressor genes on 6q within RCD1, RCD2, and RCD3; they also showed associations between RCDs in 6q and subsets of NHL, including a specific association between a group of well-differentiated lymphoid neoplasms and RCD3. The apparent heterogeneity of breakpoints when all NHLs are considered together explains the inability of previous studies to reliably establish correlations between recurring 6q deletions and histologic and clinical features of NHL.
6q缺失常见于淋巴样肿瘤，与非霍奇金淋巴瘤（NHL）的组织学和临床亚型相关。我们最近对NHL中6q位点杂合性缺失的分析显示了两个最小分子缺失区域（RMD），一个位于6q25 - 27的RMD1和一个位于6q21 - 23的RMD2。为了建立这些RMD与6q上最小细胞遗传学缺失区域（RCD）之间的相关性，并确定RCD与临床病理特征之间的关联，我们分析了459例连续确诊的、核型异常的NHL病例中的6号染色体异常情况。其中，126例（27.5%）病例有6号染色体结构异常，其中94例为缺失。对这些缺失的分析确定了三个RCD。在45例中级NHL中可见一个包含6q25 - 27的RCD1。在11例高级NHL中观察到位于6q21的RCD2，其中9例为免疫母细胞亚型。在18例缺乏t(14;18)易位的低级NHL中发现了位于6q23的RCD3。在这18例病例中，12例为小淋巴细胞NHL，其中2例中del(6q)是唯一的核型异常。在20例有t(14;18)的低级NHL病例中，缺失跨越了RCD1和RCD3。这些数据表明在RCD1、RCD2和RCD3内的6q上至少存在3个肿瘤抑制基因；它们还显示了6q上的RCD与NHL亚型之间的关联，包括一组高分化淋巴样肿瘤与RCD3之间的特定关联。当将所有NHL病例一起考虑时，断点的明显异质性解释了先前研究无法可靠地建立复发性6q缺失与NHL的组织学和临床特征之间相关性的原因。
