Cigudosa J C, Parsa N Z, Louie D C, Filippa D A, Jhanwar S C, Johansson B, Mitelman F, Chaganti R S
Laboratory of Cancer Genetics, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Genes Chromosomes Cancer. 1999 Jun;25(2):123-33.
Cytogenetic analysis was performed on 363 biopsy specimens with histologically confirmed diffuse large B-cell lymphoma (DLBCL), consecutively ascertained at the Memorial Sloan-Kettering Cancer Center, New York, between 1984 and 1994. Among 248 samples successfully karyotyped, clonal chromosomal abnormalities were noted in 215 (87%). The salient cytogenetic features of DLBCL from this analysis comprised the following. Breakpoints clustered, in decreasing frequency, at 10 recurring sites: 14q32, 18q21, 1q21, 3q27, 1p36, 8q24, 3p21, 6q21, 1p22, and 22q11. Of these, deletion breaks affecting bands 3p2 and 1p22 and translocation breaks affecting bands 14q32, 3q27, and 1q2 were frequent and distinctive for this subset of lymphomas. Translocations affecting band 14q32 were noted in 110 cases (51%) of which 42 (20%) had t(14;18)(q32;q21), 21 (10%) had t(8;14)(q24;q32) or t(8;22)(q24;q11), 14 (6.5%) had t(3;14)(q27;q32) or t(3;22)(q27;q11), and 33 (15%) had other rearrangements of 14q32. Among 144 new translocations detected in the entire group, the breakpoints in 19 were recurrent and clustered at three sites: 1q21, 3q27, and 14q32. Regions of common cytogenetic deletions were identified at 11 sites, 1p36, 1p33-34, 1p31, 1q32, 3p25-26, 3p21, 3q21, 6q15, 6q21, 6q23-24, and 7q32, suggesting possible loss of candidate tumor suppressor genes associated with DLBCL development. Of these, only those at 6q21, 6q23, and 7q32 have previously been described in lymphoid neoplasms. The group of DLBCL with translocations affecting band 14q32 showed a significantly different pattern of additional cytogenetic changes compared to the group lacking such translocation. This new comprehensive cytogenetic characterization provides the basis for investigations aimed at identifying molecular mechanisms as well as the clinical impact of cytogenetic changes in DLBCL.
对1984年至1994年间在纽约纪念斯隆凯特琳癌症中心连续确诊的363例经组织学证实的弥漫性大B细胞淋巴瘤（DLBCL）活检标本进行了细胞遗传学分析。在248个成功进行核型分析的样本中，215个（87%）发现了克隆性染色体异常。本次分析中DLBCL的主要细胞遗传学特征如下。断点按频率递减依次聚集在10个重复位点：14q32、18q21、1q21、3q27、1p36、8q24、3p21、6q21、1p22和22q11。其中，影响3p2和1p22带的缺失断点以及影响14q32、3q27和1q2带的易位断点在该淋巴瘤亚组中较为常见且具有特征性。在110例（51%）病例中发现了影响14q32带的易位，其中42例（20%）为t(14;18)(q32;q21)，21例（10%）为t(8;14)(q24;q32)或t(8;22)(q24;q11)，14例（6.5%）为t(3;14)(q27;q32)或t(3;22)(q27;q11)，33例（15%）为14q32的其他重排。在整个研究组检测到的144个新易位中，19个断点具有重复性且聚集在三个位点：1q21、3q27和14q32。在11个位点发现了常见的细胞遗传学缺失区域，分别为1p36、1p33 - 34、1p31、1q32、3p25 - 26、3p21、3q21、6q15、6q21、6q23 - 24和7q32，提示可能存在与DLBCL发生相关的候选抑癌基因缺失。其中，只有6q21、6q23和7q32的缺失区域此前在淋巴肿瘤中有所描述。与缺乏此类易位的组相比，影响14q32带易位的DLBCL组在其他细胞遗传学改变模式上存在显著差异。这一新的全面细胞遗传学特征为旨在确定DLBCL细胞遗传学改变的分子机制及其临床影响的研究提供了基础。
