Mutations or copy number losses of <i>CD58</i> and <i>TP53</i> genes in diffuse large B cell lymphoma are independent unfavorable prognostic factors

Abstract

// Yang Cao 1, * , Tao Zhu 1, * , Peiling Zhang 1 , Min Xiao 1 , Shuhua Yi 2 , Yan Yang 1 , Qinlu Li 1 , Shaoping Ling 3 , Yafei Wang 4 , Lili Gao 1 , Li Zhu 1 , Jue Wang 1 , Na Wang 1 , Liang Huang 1 , Peihong Zhang 2 , Qiongli Zhai 4 , Lugui Qiu 2 , Jianfeng Zhou 1, 2 1 Department of Hematology &amp; Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China 2 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, P.R. China 3 Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, P.R. China 4 Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, P.R. China * These authors have contributed equally to this work Correspondence to: Jianfeng Zhou, email: jfzhou@tjh.tjmu.edu.cn Lugui Qiu, email: drqiu99@medmail.com.cn Keywords: TP53, CD58, mutation, copy number loss, DLBCL Received: September 24, 2015&emsp;&emsp;&emsp;&emsp; Accepted: September 02, 2016&emsp;&emsp;&emsp;&emsp; Published: November 4, 2016 ABSTRACT The advent of next generation sequencing (NGS) technologies has expedited the discovery of novel genetic lesions in DLBCL. The prognostic significance of these identified gene mutations is largely unknown. In this study, we performed NGS for the 27 genes most frequently implicated in 196 patients. Interestingly, TP53 mutations were found to be significantly more common in DLBCL with MYC translocations ( r = 0.446, P = 0.034). While no gene mutation was found to be more prevalent in patients with DLBCL with bone marrow involvement, MYD88 mutations were more common in primary DLBCL of the CNS or testis. To evaluate the prognostic significance of the abnormalities of these 27 genes, a total of 165 patients with newly diagnosed DLBCL, NOS were included in a multivariate survival analysis. Surprisingly, in addition to the TP53 mutation, CD58 mutation was found to predict poor clinical outcome. Furthermore, copy number loss of CD58 or TP53 was also identified to be an independent negative prognostic factor. Our results have uncovered the previously unknown critical impact of gene mutations on the prognosis of DLBCL and are fundamentally important for the future design of tailored therapy for improved clinical outcomes.