PRAD1, A CANDIDATE BCL1 ONCOGENE - MAPPING AND EXPRESSION IN CENTROCYTIC LYMPHOMA
PRAD1, A CANDIDATE BCL1 ONCOGENE - MAPPING AND EXPRESSION IN CENTROCYTIC LYMPHOMA
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DOI：
10.1073/pnas.88.21.9638
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发表时间：
1991-11-01
影响因子：
11.1
通讯作者：
ARNOLD, A
中科院分区：
文献类型：
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作者：
ROSENBERG, CL;WONG, E;ARNOLD, A
染色体11q13上BCL1(B细胞淋巴瘤1)区域的重排似乎是中心性淋巴瘤的高度特征，在其他B细胞肿瘤中也很少见。重排被认为解除了附近的原癌基因的调控，但BCL1断裂点附近的转录序列尚未确定。PRAD1，以前被命名为D11S287E，在11q13被鉴定为在甲状旁腺腺瘤中与甲状旁腺激素基因重排的染色体断裂区；这个高度保守的假定癌基因编码一个新的周期蛋白，已与bcl1连锁，并与11q13扩增的乳腺和鳞状细胞肿瘤的亚型有关。我们报告了脉冲场凝胶电泳数据，显示BCL1和PRAD1之间的距离不超过130千碱基。PRAD1mRNA在7例中心细胞性淋巴瘤中有7例大量表达，而在13例密切相关的非中心细胞性淋巴瘤中有表达。7例中心性淋巴瘤中有3例可检测到bcl1 DNA重排。此外，与5个CLL对照相比，两个罕见的带有BCL1重排的CLL过表达PRAD1。因此，PRAD1是一个很好的候选“bcl1癌基因”。它的过度表达可能是B细胞肿瘤中BCL1附近重排的一个关键结果，也是中心性淋巴瘤的一个统一的病理特征。
Rearrangement of the BCL1 (B-cell lymphoma 1) region on chromosome 11q13 appears to be highly characteristic of centrocytic lymphoma and also is found infrequently in other B-cell neoplasms. Rearrangement is thought to deregulate a nearby protooncogene, but transcribed sequences in the immediate vicinity of BCL1 breakpoints had not been identified. PRAD1, previously designated D11S287E, was identified on 11q13 as a chromosomal breakpoint region rearranged with the parathyroid hormone gene in a subset of parathyroid adenomas; this highly conserved putative oncogene, which encodes a novel cyclin, has been linked to BCL1 and implicated also in subsets of breast and squamous cell neoplasms with 11q13 amplification. We report pulsed-field gel electrophoresis data showing BCL1 and PRAD1 to be no more than 130 kilobases apart. PRAD1 mRNA is abundantly expressed in seven of seven centrocytic lymphomas (Kiel classification), in contrast to 13 closely related but noncentrocytic lymphomas. Three of the seven centrocytic lymphomas had detectable BCL1 DNA rearrangement. Also, two unusual cases of CLL with BCL1 rearrangement overexpressed PRAD1, in contrast to five CLL controls. Thus, PRAD1 is an excellent candidate "BCL1 oncogene." Its overexpression may be a key consequence of rearrangement of the BCL1 vicinity in B-cell neoplasms and a unifying pathogenetic feature in centrocytic lymphoma.