Haberl Sabine, Haferlach Torsten, Stengel Anna, Jeromin Sabine, Kern Wolfgang, Haferlach Claudia
MLL Munich Leukemia Laboratory, Munich, Germany.
MLL Munich Leukemia Laboratory, Munich, Germany.
Cancer Genet. 2016 Oct;209(10):431-439. doi: 10.1016/j.cancergen.2016.08.007. Epub 2016 Sep 14.
A cohort comprising 156 patients with B-cell neoplasms harboring an MYC rearrangement was analyzed with respect to phenotypic presentation, molecular markers (TP53, MYC and ID3) and additional cytogenetic abnormalities (concomitantly occurring BCL2, BCL6 and/or CCND1 rearrangements; double, triple or quadruple hit lymphomas = multiple hit lymphomas). MYC translocations occurred as single hit (only MYC rearranged, 63%) or multiple hit lymphoma (37%) and presented as acute leukemia (AL) (14%), Burkitt lymphoma (30%), chronic lymphocytic leukemia (CLL) (21%) or other mature B-cell neoplasms (35%). Multiple hit lymphomas more frequently showed a complex karyotype compared to single hit lymphomas (62% vs. 28%, p < 0.001). Single hit Burkitt lymphomas presented with specific characteristics, by translocation of MYC to an immunoglobulin locus, predominantly a non-complex karyotype (23% vs. 67%, p = 0.012) and a significantly higher ID3 and TP53 mutation frequency (ID3mut: 49% vs. 0%, p = 0.002; TP53mut: 69% vs. 33%, p = 0.045). Additionally, MYC rearranged CLL presented as outstanding group by often showing a non-complex karyotype (85%), absence of ID3 mutations, a high frequency of SF3B1 mutations, and a frequent involvement of non-immunoglobulin loci as MYC-partner genes (61%). Consequently, genetic characteristics distinguish different subgroups of MYC rearranged B-cell neoplasms and therefore may contribute to a new classification system.
对156例携带MYC重排的B细胞肿瘤患者组成的队列进行了分析，涉及表型表现、分子标志物（TP53、MYC和ID3）以及其他细胞遗传学异常（同时发生的BCL2、BCL6和/或CCND1重排；双打击、三打击或四打击淋巴瘤=多打击淋巴瘤）。MYC易位表现为单打击（仅MYC重排，63%）或多打击淋巴瘤（37%），并表现为急性白血病（AL）（14%）、伯基特淋巴瘤（30%）、慢性淋巴细胞白血病（CLL）（21%）或其他成熟B细胞肿瘤（35%）。与单打击淋巴瘤相比，多打击淋巴瘤更常表现为复杂核型（62%对28%，p<0.001）。单打击伯基特淋巴瘤具有特定特征，即MYC易位至免疫球蛋白基因座，主要为非复杂核型（23%对67%，p=0.012），且ID3和TP53突变频率显著更高（ID3突变：49%对0%，p=0.002；TP53突变：69%对33%，p=0.045）。此外，MYC重排的CLL表现为一个突出的组，常显示非复杂核型（85%），无ID3突变，SF3B1突变频率高，且作为MYC伙伴基因的非免疫球蛋白基因座频繁受累（61%）。因此，遗传特征可区分MYC重排的B细胞肿瘤的不同亚组，因此可能有助于建立新的分类系统。
