非霍奇金氏淋巴瘤恶性度高，预后差，发病机制复杂，染色体易位是最常见的标志性改变，其发生可能与淋巴细胞发育成熟过程的基因重组异常有关。XLF在DNA损伤修复中作为非同源末端连接的核心成员，连接DNA断端，XLF胚系突变可引起基因组不稳定。前期研究报道了世界首例中国弥漫大B细胞性淋巴瘤肿瘤细胞中发现XLF体细胞突变，同时发现两种涉及免疫球蛋白重链的染色体易位和类别转换重组异常(J Exp Med，2012,209:291-305)。然而，XLF突变对染色体易位、淋巴瘤致病机制并不明确。在此研究基础上，本课题拟探讨XLF缺陷淋巴细胞中染色体断裂易位发生情况和易位DNA修复机制改变，进一步研究XLF缺陷淋巴细胞癌变能力，确定XLF突变在淋巴瘤发生发展中的作用，以及对染色体易位的影响。通过本研究，有望确定XLF在淋巴瘤发生发展中的抑癌作用，为淋巴瘤发病机制研究提供新思路，为淋巴瘤治疗寻求新靶点。

Non-Hodgkin lymphoma (NHL) was aggressive and of poor outcome.The etiology was complicated. Chromosomal translocation was the hallmarker for NHL, which may result from the aberrant recombination during the development of lymphocyte. XLF (also called Cernunnos) was a critical factor for non-homologous end joining (NHEJ) via DNA end joining when responding to DNA damage and repair. The germline mutation of XLF caused genomic instability. Our preliminary results found the first somatic mutation of XLF and abberrant class switch recombination in one Chinese diffuse large B cell lymphoma tumor cells. Simutaneously, double hits chromosomal translocations involving immunoglobulin heavy chain loci was detected in tumor cells (J Exp Med,2012,209:291-305).But the mechanism of XLF deficiency in lymphomagenesis and chromosomal translocation is yet to known. Based on these results, we are to explore chromosomal breaks and translocations in XLF deficienct lymphocyte. Furthermore to investigate the mechanismic change of DNA repair in the loci of chromosomal translocations and the ability of oncogenesis in XLF deficient lymphcyte, to elucidate the role of XLF in the etiology of lymphoma. This project will confirm the suppression function of XLF in chromosomal translocation and lymphomagenesis, to provide the new insight in the field of lymphoma etiology, and to provide a new therapeutic target for lymphoma treatment.