Yano T, van Krieken J H, Magrath I T, Longo D L, Jaffe E S, Raffeld M
Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD 20892.
Blood. 1992 Mar 1;79(5):1282-90.
To assess the biologic relevance of the morphologic distinctions between subtypes of small noncleaved cell lymphomas (SNCL), ie, the sporadic Burkitt's type (sBT) and the non-Burkitt's type (nBT), we have examined the molecular organization of several lymphomagenic oncogenes (c-myc, bcl-1, bcl-2) and the potential pathogenetic contribution of the Epstein-Barr virus (EBV). Twenty-nine cases of SNCL, not associated with immunodeficiency syndromes, were reviewed and classified as sBT (18 cases) or nBT (11 cases) without knowledge of the clinical or molecular data. Southern blot analysis of 18 sBTs found 17 to contain c-myc rearrangements. Fifteen of these comigrated with an Ig heavy-chain gene segment, indicating t(8;14) translocation. Chromosome 8 breakpoints were clustered in the first exon and the first intron of the c-myc gene. Chromosome 14 breakpoints mapped to the JH locus in three tumors, the S mu locus in nine tumors, and the S alpha locus in the remaining three tumors. Cases involving the S alpha locus appeared to have a more rapid clinical course. All sBTs possessed germline bcl-2 and bcl-1 gene fragments. In contrast, Southern blot analysis of 11 nBTs found none with c-myc rearrangements. Rather, three of 10 evaluable nBTs had bcl-2 rearrangements. The remaining seven showed no evidence of involvement by any of the lymphoma-associated oncogene/breakpoint regions studied. EBV genome was detected in two sBTs and in one nBT, and thus was not a distinguishing feature. These results indicate that the subtle histologic differences that distinguish subcategories of SNCL are significant biologically and reflect distinct molecular mechanisms of lymphomagenesis. Furthermore, the data suggest that the nBTs comprise a heterogeneous group with respect to their molecular genetic composition and confirm the remarkable molecular genetic homogeneity of the sBT group.
为评估小无裂细胞淋巴瘤（SNCL）各亚型，即散发性伯基特型（sBT）和非伯基特型（nBT）之间形态学差异的生物学相关性，我们检测了几种致淋巴瘤癌基因（c-myc、bcl-1、bcl-2）的分子结构以及爱泼斯坦-巴尔病毒（EBV）的潜在致病作用。回顾了29例与免疫缺陷综合征无关的SNCL病例，并在不了解临床或分子数据的情况下将其分类为sBT（18例）或nBT（11例）。对18例sBT进行Southern印迹分析，发现17例含有c-myc重排。其中15例与免疫球蛋白重链基因片段共迁移，表明存在t(8;14)易位。8号染色体断点聚集在c-myc基因的第一个外显子和第一个内含子中。14号染色体断点在3个肿瘤中定位于JH基因座，9个肿瘤中定位于Sμ基因座，其余3个肿瘤中定位于Sα基因座。涉及Sα基因座的病例似乎临床病程更快。所有sBT均具有种系bcl-2和bcl-1基因片段。相比之下，对11例nBT进行Southern印迹分析，未发现c-myc重排。相反，10例可评估的nBT中有3例存在bcl-2重排。其余7例未显示出所研究的任何淋巴瘤相关癌基因/断点区域受累的证据。在2例sBT和1例nBT中检测到EBV基因组，因此它不是一个区分特征。这些结果表明，区分SNCL亚类的细微组织学差异在生物学上具有重要意义，并反映了淋巴瘤发生的不同分子机制。此外，数据表明nBT在分子遗传组成方面是一个异质性群体，并证实了sBT群体显著的分子遗传同质性。
