Lo Coco F, Gaidano G, Louie D C, Offit K, Chaganti R S, Dalla-Favera R
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Blood. 1993 Oct 15;82(8):2289-95.
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.
大多数低度非霍奇金淋巴瘤（NHL）会向中度和高度淋巴瘤发生临床进展。这种进展通常与组织学从滤泡型向弥漫型NHL的转变有关。目前尚不清楚这种演变背后的致病机制。在本研究中，我们分析了影响原癌基因和肿瘤抑制基因的相关基因损伤在NHL进展中的作用。对21例有临床进展且有（5例）或无（16例）组织学转变证据的患者进行序贯活检，分析其核型变化、c-myc重排以及通过Southern印迹分析检测影响6q27的缺失，通过单链构象多态性（SSCP）分析并结合聚合酶链反应扩增产物的直接测序检测p53突变。未检测到与进展相关的新的细胞遗传学异常，所有分析样本的c-myc基因均正常。在5例显示从滤泡型向弥漫型NHL组织学转变的病例中，有4例检测到p53基因突变，而在16例无组织学转变的临床进展病例中均未检测到p53基因突变。在其中1例阳性病例中，相同的突变也存在于转变前的活检中，这与主要为滤泡型模式内存在弥漫型区域相关。在其中1例病例中，在转变后的活检中还检测到6q27缺失以及p53突变。这些发现表明，p53突变与滤泡性淋巴瘤的组织学转变相关，并且可能是其原因。
