Salaverria Itziar, Zettl Andreas, Beà Silvia, Hartmann Elena M, Dave Sandeep S, Wright George W, Boerma Evert-Jan, Kluin Philip M, Ott German, Chan Wing C, Weisenburger Dennis D, Lopez-Guillermo Armando, Gascoyne Randy D, Delabie Jan, Rimsza Lisa M, Braziel Rita M, Jaffe Elaine S, Staudt Louis M, Müller-Hermelink Hans Konrad, Campo Elias, Rosenwald Andreas
Institute of Pathology, University of Würzburg, Josef-Schneider-Str. 2 97080 Würzburg, Germany.
Haematologica. 2008 Sep;93(9):1327-34. doi: 10.3324/haematol.13071. Epub 2008 Aug 12.
Burkitt's lymphoma is an aggressive B-cell lymphoma characterized by typical morphological, immunophenotypic and molecular features. Gene expression profiling provided a molecular signature of Burkitt's lymphoma, but also demonstrated that a subset of aggressive B-cell lymphomas not fulfilling the current World Health Organization criteria for the diagnosis of Burkitt's lymphoma nonetheless show a molecular signature of Burkitt's lymphoma ('discrepant Burkitt's lymphoma'). Given the different treatment of Burkitt's lymphoma and diffuse large B-cell lymphomas we investigated molecular differences within gene expression-defined Burkitt's lymphoma.
We studied tumors from 51 Burkitt's lymphoma patients, comprising 26 with classic Burkitt's lymphoma, 17 with atypical Burkitt's lymphoma and 8 with 'discrepant Burkitt's lymphoma', by comparative genomic hybridization and gene expression profiling.
Classic and atypical Burkitt's lymphoma (excluding 'discrepant Burkitt's lymphoma'), in adult and pediatric cases do not differ in underlying genomic imbalances or gene expression suggesting that these subgroups are molecularly homogeneous. 'Discrepant Burkitt's lymphoma', however, differ dramatically in the absolute number of alterations from classic/atypical Burkitt's lymphoma and from diffuse large B-cell lymphoma. Moreover, this category includes lymphomas that carry both the t(14;18) and t(8;14) translocations and are clinically characterized by presentation in adult patients and an aggressive course.
Pediatric and adult Burkitt's lymphoma are molecularly homogeneous, whereas 'discrepant Burkitt's lymphoma' differ in underlying genetic and clinical features from typical/atypical Burkitt's lymphoma. 'Discrepant Burkitt's lymphoma' may therefore form a distinct genetic subgroup of aggressive B-cell lymphomas, which show poor response to multi-agent chemotherapy.
伯基特淋巴瘤是一种侵袭性B细胞淋巴瘤,具有典型的形态学、免疫表型和分子特征。基因表达谱分析不仅揭示了伯基特淋巴瘤的分子特征,还表明一部分不符合世界卫生组织目前伯基特淋巴瘤诊断标准的侵袭性B细胞淋巴瘤,却显示出伯基特淋巴瘤的分子特征(“不一致性伯基特淋巴瘤”)。鉴于伯基特淋巴瘤和弥漫性大B细胞淋巴瘤的治疗方法不同,我们研究了基因表达定义的伯基特淋巴瘤内部的分子差异。
我们通过比较基因组杂交和基因表达谱分析,研究了51例伯基特淋巴瘤患者的肿瘤,其中包括26例经典伯基特淋巴瘤、17例非典型伯基特淋巴瘤和8例“不一致性伯基特淋巴瘤”。
经典和非典型伯基特淋巴瘤(不包括“不一致性伯基特淋巴瘤”),在成人和儿童病例中,其潜在的基因组失衡或基因表达并无差异,这表明这些亚组在分子水平上是同质的。然而,“不一致性伯基特淋巴瘤”与经典/非典型伯基特淋巴瘤以及弥漫性大B细胞淋巴瘤在改变的绝对数量上有显著差异。此外,这一类别包括同时携带t(14;18)和t(8;14)易位的淋巴瘤,其临床特征为成年患者发病且病程侵袭性。
儿童和成人伯基特淋巴瘤在分子水平上是同质的,而“不一致性伯基特淋巴瘤”在潜在的遗传和临床特征上与典型/非典型伯基特淋巴瘤不同。因此,“不一致性伯基特淋巴瘤”可能构成侵袭性B细胞淋巴瘤的一个独特遗传亚组,对多药化疗反应不佳。