Hummel Michael, Bentink Stefan, Berger Hilmar, Klapper Wolfram, Wessendorf Swen, Barth Thomas F E, Bernd Heinz-Wolfram, Cogliatti Sergio B, Dierlamm Judith, Feller Alfred C, Hansmann Martin-Leo, Haralambieva Eugenia, Harder Lana, Hasenclever Dirk, Kühn Michael, Lenze Dido, Lichter Peter, Martin-Subero Jose Ignacio, Möller Peter, Müller-Hermelink Hans-Konrad, Ott German, Parwaresch Reza M, Pott Christiane, Rosenwald Andreas, Rosolowski Maciej, Schwaenen Carsten, Stürzenhofecker Benjamin, Szczepanowski Monika, Trautmann Heiko, Wacker Hans-Heinrich, Spang Rainer, Loeffler Markus, Trümper Lorenz, Stein Harald, Siebert Reiner
Institute of Pathology, Campus Benjamin Franklin, Charité Universitätsmedizin, Berlin, Germany.
N Engl J Med. 2006 Jun 8;354(23):2419-30. doi: 10.1056/NEJMoa055351.
The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is unclear. We used transcriptional and genomic profiling to define Burkitt's lymphoma more precisely and to distinguish subgroups in other types of mature aggressive B-cell lymphomas.
We performed gene-expression profiling using Affymetrix U133A GeneChips with RNA from 220 mature aggressive B-cell lymphomas, including a core group of 8 Burkitt's lymphomas that met all World Health Organization (WHO) criteria. A molecular signature for Burkitt's lymphoma was generated, and chromosomal abnormalities were detected with interphase fluorescence in situ hybridization and array-based comparative genomic hybridization.
We used the molecular signature for Burkitt's lymphoma to identify 44 cases: 11 had the morphologic features of diffuse large-B-cell lymphomas, 4 were unclassifiable mature aggressive B-cell lymphomas, and 29 had a classic or atypical Burkitt's morphologic appearance. Also, five did not have a detectable IG-myc Burkitt's translocation, whereas the others contained an IG-myc fusion, mostly in simple karyotypes. Of the 176 lymphomas without the molecular signature for Burkitt's lymphoma, 155 were diffuse large-B-cell lymphomas. Of these 155 cases, 21 percent had a chromosomal breakpoint at the myc locus associated with complex chromosomal changes and an unfavorable clinical course.
Our molecular definition of Burkitt's lymphoma clarifies and extends the spectrum of the WHO criteria for Burkitt's lymphoma. In mature aggressive B-cell lymphomas without a gene signature for Burkitt's lymphoma, chromosomal breakpoints at the myc locus were associated with an adverse clinical outcome.
伯基特淋巴瘤与弥漫性大B细胞淋巴瘤之间的区别尚不清楚。我们利用转录组和基因组分析更精确地定义伯基特淋巴瘤，并区分其他类型成熟侵袭性B细胞淋巴瘤的亚组。
我们使用Affymetrix U133A基因芯片对220例成熟侵袭性B细胞淋巴瘤的RNA进行基因表达谱分析，其中包括一组符合世界卫生组织（WHO）所有标准的8例伯基特淋巴瘤核心病例。生成了伯基特淋巴瘤的分子特征，并通过间期荧光原位杂交和基于阵列的比较基因组杂交检测染色体异常。
我们利用伯基特淋巴瘤的分子特征鉴定出44例病例：11例具有弥漫性大B细胞淋巴瘤的形态学特征，4例为无法分类的成熟侵袭性B细胞淋巴瘤，29例具有经典或非典型伯基特淋巴瘤的形态学表现。此外，5例未检测到IG-myc伯基特易位，而其他病例含有IG-myc融合，大多为简单核型。在176例没有伯基特淋巴瘤分子特征的淋巴瘤中，155例为弥漫性大B细胞淋巴瘤。在这155例病例中，21%在myc基因座有染色体断点，伴有复杂的染色体变化和不良的临床病程。
我们对伯基特淋巴瘤的分子定义明确并扩展了WHO伯基特淋巴瘤标准的范围。在没有伯基特淋巴瘤基因特征的成熟侵袭性B细胞淋巴瘤中，myc基因座的染色体断点与不良临床结局相关。
