The genetic landscape of mutations in Burkitt lymphoma. Homo sapiens

Burkitt lymphoma is characterized by deregulation of MYC, but the contribution of other genetic mutations to the disease is largely unknown. Here, we describe the first completely sequenced genome from a Burkitt lymphoma tumor and germline DNA from the same affected individual. We further sequenced the exomes of 59 Burkitt lymphoma tumors and compared them to sequenced exomes from 94 diffuse large B-cell lymphoma (DLBCL) tumors. We identified 70 genes that were recurrently mutated in Burkitt lymphomas, including ID3, GNA13, RET, PIK3R1 and the SWI/SNF genes ARID1A and SMARCA4. Our data implicate a number of genes in cancer for the first time, including CCT6B, SALL3, FTCD and PC. ID3 mutations occurred in 34% of Burkitt lymphomas and not in DLBCLs. We show experimentally that ID3 mutations promote cell cycle progression and proliferation. Our work thus elucidates commonly occurring gene-coding mutations in Burkitt lymphoma and implicates ID3 as a new tumor suppressor gene. Overall design: Gene expression profiling on 21 Burkitt lymphomas was performed using standard Affymetrix protocols as described previously. Briefly, 1 μg of total RNA was reverse transcribed, using oligo(dT) primer to synthesize cDNA. T7 primer was used for in vitro transcription, resulting in labeled cRNA, which was fragmented and hybridized to Affymetrix Whole-Genome Gene 1.0 ST microarrays. Microarrays were washed and scanned, and the data were normalized as described previously.

伯基特淋巴瘤（Burkitt lymphoma）以MYC基因失调为特征，但其他遗传突变对该疾病的贡献在很大程度上仍未明确。本研究首次报道了1例伯基特淋巴瘤肿瘤组织及同一患者生殖系DNA的全基因组测序结果。本研究进一步对59例伯基特淋巴瘤肿瘤组织的外显子组进行测序，并将其与94例弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma, DLBCL）的外显子组测序数据进行比对分析。本研究共鉴定出70个在伯基特淋巴瘤中存在复发性突变的基因，包括ID3、GNA13、RET、PIK3R1以及SWI/SNF复合物相关基因ARID1A和SMARCA4。本研究数据首次将多个基因与癌症发生关联，其中包括CCT6B、SALL3、FTCD及PC。ID3突变在34%的伯基特淋巴瘤样本中被检测到，而在弥漫大B细胞淋巴瘤中未发现此类突变。本研究通过实验证实，ID3突变可促进细胞周期进程与细胞增殖。综上，本研究阐明了伯基特淋巴瘤中常见的基因编码突变，并证实ID3是一个新型肿瘤抑制基因。实验设计：本研究按照此前报道的标准Affymetrix实验流程，对21例伯基特淋巴瘤样本进行了基因表达谱分析。简要而言，实验步骤为：取1μg总RNA，以寡聚dT（oligo(dT)）引物逆转录合成互补DNA（cDNA）；随后采用T7引物进行体外转录，得到标记后的互补RNA（cRNA），将其片段化后与Affymetrix全基因组基因1.0 ST微阵列进行杂交。微阵列经洗涤、扫描后，按照此前报道的方法对数据进行标准化处理。