p53 mutations are associated with histologic transformation of follicular lymphoma.
p53 mutations are associated with histologic transformation of follicular lymphoma.
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DOI：
10.1182/blood.v82.8.2289.bloodjournal8282289
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发表时间：
1993-10
期刊：
影响因子：
20.3
通讯作者：
F. Coco;G. Gaidano;Diane;Louie;K. Offit;R. Chaganti;R. Dalla-Favera
中科院分区：
文献类型：
--
作者：
F. Coco;G. Gaidano;Diane;Louie;K. Offit;R. Chaganti;R. Dalla-Favera
大多数低度恶性非霍奇金淋巴瘤(NHL)的临床进展为中、高度恶性。这种进展通常与组织学上从滤泡型向弥漫型NHL的转变有关。这种进化背后的致病机制目前尚不清楚。在这项研究中，我们分析了影响原癌基因和抑癌基因的相关基因损伤在NHL进展中的作用。应用单链构象多态性(SSCP)分析和聚合酶链式反应扩增产物直接测序相结合的方法，对21例有组织学改变(5例)和无组织学改变(16例)的临床进展期患者进行了核型分析、影响6q27的c-myc重排和缺失分析，以及p53基因突变分析。没有发现与疾病进展相关的新的细胞遗传学异常，所有分析的样本都显示出正常的c-myc基因。从滤泡型向弥漫型转化的5例NHL中有4例检测到p53基因突变，16例无组织学转化而临床进展的NHL中均未检测到p53基因突变。在这些阳性病例中，1例在转化前活检中也存在相同的突变，这与主要滤泡模式中弥漫型区域的存在有关。在其中1例中，在转化后活检组织中还检测到6q27缺失和p53突变。这些发现表明，P53突变与滤泡性淋巴瘤的组织学转化有关，并可能与其相关。
The majority of low-grade non-Hodgkin's lymphomas (NHL) undergo clinical progression toward intermediate- and high-grade lymphomas. This progression is often associated with histologic transformation from follicular to diffuse-type NHL. The pathogenetic mechanisms underlying this evolution are presently unknown. In this study, we have analyzed the role in NHL progression of relevant genetic lesions affecting proto-oncogenes and tumor suppressor genes. Sequential biopsies from 21 patients with clinical progression with (5 cases) or without (16 cases) evidence of histologic transformation were analyzed for karyotypic changes, c-myc rearrangements and deletions affecting 6q27 by Southern blot analysis, and p53 mutations by single-strand conformation polymorphism (SSCP) analysis coupled with direct sequencing of polymerase chain reaction-amplified products. No novel cytogenetic aberration was detected in association with progression, and all samples analyzed displayed a normal c-myc gene. Mutations of the p53 gene were detected in 4 of 5 cases displaying histologic transformation from follicular to diffuse-type NHL and in none of the 16 cases displaying clinical progression in the absence of histologic transformation. In 1 of these positive cases, the same mutation was also present in the pretransformation biopsy, correlating with the presence of diffuse-type areas within a predominant follicular pattern. In 1 of these cases, a deletion of 6q27 was also detected in the posttransformation biopsy along with a p53 mutation. These findings indicate that p53 mutations are associated with and may be responsible for histologic transformation of follicular lymphoma.