Ladanyi M, Offit K, Jhanwar S C, Filippa D A, Chaganti R S
Laboratory of Cancer Genetics, Sloan-Kettering Institute, New York, NY.
Blood. 1991 Mar 1;77(5):1057-63.
The configuration of the MYC gene in diffuse large cell lymphomas (DLCL) with translocations involving band 8q24 [t(8q24)] has not been systematically studied. We collected cytogenetic and clinical data on 171 consecutive cases of DLCL, including cleaved, noncleaved, and immunoblastic types, of which 96 had DNA available and 124 had abnormal karyotypes. The cases with DNA available were evaluated for MYC rearrangement (MYC-R) by Southern hybridization of EcoRI-digested tumor DNA using an exon-1 probe, a combination of probe and enzyme known to detect over 85% of breaks in sporadic Burkitt's lymphoma. In cases studied at diagnosis, MYC-R, t(8;14)(q24;q32), or other t(8q24) were not prognostically significant. Among the 124 cases with karyotypic abnormalities, seropositivity for human immunodeficiency virus was significantly more common in cases with a t(8q24) (72%) than in cases without it (9%) (P less than .05). Of the four cases with an MYC -R, two had a t(8;14), one had a t(7;8;14)(p15;q24;q32), and one had a t(8;?)(q24;?) and a del(8)(q24). In the three previous cases with translocations involving 8q24 and 14q32, comigration of the rearranged MYC band with either the J region or the switch-mu region of the Ig heavy chain gene could not be demonstrated, leaving the 14q32 breakpoint undefined at the molecular level. Among the remaining 72 cases where both an abnormal karyotype and molecular data were available, 11 had a t(8q24), either t(8;14) or t(8;22)(q24;q11), in the absence of an MYC-R. In these cases, the 8q24 break was presumably located outside of the EcoRI MYC fragment. All 15 cases with a t(8q24) were also screened for point mutations in the PvuII site in the first exon of MYC; two cases that were not MYC-R showed loss of this restriction site. These results indicate that in most DLCL with t(8;14) or other t(8q24), the 8q24 breakpoint lies away from the MYC gene; in a minority of these cases, point mutations in regulatory noncoding regions were detected.
对于伴有涉及8q24带易位[t(8q24)]的弥漫性大细胞淋巴瘤(DLCL)中MYC基因的结构，尚未进行系统研究。我们收集了171例连续的DLCL病例的细胞遗传学和临床数据，包括裂细胞型、非裂细胞型和免疫母细胞型，其中96例有可用的DNA，124例有异常核型。对有可用DNA的病例，使用外显子1探针通过EcoRI消化的肿瘤DNA的Southern杂交评估MYC重排(MYC-R)，该探针和酶的组合已知可检测散发性伯基特淋巴瘤中超过85%的断裂点。在诊断时研究的病例中，MYC-R、t(8;14)(q24;q32)或其他t(8q24)在预后方面无显著意义。在124例有核型异常的病例中，人类免疫缺陷病毒血清阳性在有t(8q24)的病例中(72%)比没有t(8q24)的病例中(9%)更常见(P<0.05)。在4例有MYC-R的病例中，2例有t(8;14)，1例有t(7;8;14)(p15;q24;q32)，1例有t(8;?)(q24;?)和del(8)(q24)。在之前3例涉及8q24和14q32易位的病例中，无法证明重排的MYC带与Ig重链基因的J区或转换μ区共迁移，在分子水平上14q32断裂点仍未明确。在其余72例既有异常核型又有分子数据的病例中，11例有t(8q24)，即t(8;14)或t(8;22)(q24;q11)，但没有MYC-R。在这些病例中，8q24断裂点可能位于EcoRI MYC片段之外。对所有15例有t(8q24)的病例也进行了MYC第一外显子中PvuII位点的点突变筛查；2例没有MYC-R的病例显示该限制性位点缺失。这些结果表明，在大多数有t(8;14)或其他t(8q24)的DLCL中，8q24断裂点远离MYC基因；在这些病例的少数中，检测到调控非编码区的点突变。
