Study of the cancer genome in T lymphoma showing a recurrent chromosome 12 translocation

Irradiated BLOOM KO mice produced a wide range of tumours (lymphoma, leukaemia, sarcoma, and carcinoma). A pilot study has been done on primary cultures derivated from T lymphoma in order to identify genomic regions or genes that are frequently rearranged. We analysed these samples for common copy number rearrangement and translocation using respectively array CGH and multicolour FISH (in collaboration with Nigel Carter). We found that a subregion on the distal part of chromosome 12 around 108Mb which was often involved in translocation breakpoints and/or copy number alteration ( ie deletion and/or amplifications) in 40% of the samples. We think a gene in particular could be the target of all these localized rearrangements, the tumour suppressor gene Bcl11. We need genome wide parallel pair-ended sequencing to map more precisely some of the complex breakpoints we have identified and see whether any fusion protein results from these events.

经辐照的BLOOM基因敲除（knockout, KO）小鼠可产生多种类型肿瘤，包括淋巴瘤、白血病、肉瘤与癌。为鉴定频繁发生重排的基因组区域或基因，我们针对T淋巴瘤来源的原代培养物开展了一项预实验研究。我们分别借助阵列比较基因组杂交（array Comparative Genomic Hybridization, array CGH）与多色荧光原位杂交（multicolour FISH），对样本的常见拷贝数重排与易位进行了分析（与奈杰尔·卡特（Nigel Carter）合作完成）。研究发现，12号染色体远端约108 Mb的一个亚区域，在40%的样本中频繁作为易位断裂点及/或发生拷贝数改变（即缺失及/或扩增）。我们推测，其中存在一个可作为所有这些局灶性重排靶点的特定基因，即抑癌基因Bcl11。我们需要开展全基因组双端平行测序，以更精准地定位已鉴定出的部分复杂断裂点，并探究此类事件是否会产生融合蛋白。