Mutations or copy number losses of CD58 and TP53 genes in diffuse large B cell lymphoma are independent unfavorable prognostic factors
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Yang Cao1,*, Tao Zhu1,*, Peiling Zhang1, Min Xiao1, Shuhua Yi2, Yan Yang1, Qinlu Li1, Shaoping Ling3, Yafei Wang4, Lili Gao1, Li Zhu1, Jue Wang1, Na Wang1, Liang Huang1, Peihong Zhang2, Qiongli Zhai4, Lugui Qiu2, Jianfeng Zhou1,2
1Department of Hematology & Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China
2State 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
3Laboratory of Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, P.R. China
4Tianjin Cancer Hospital, Tianjin Medical University, Tianjin, P.R. China
*These authors have contributed equally to this work
Jianfeng Zhou, email: [email protected]
Lugui Qiu, email: [email protected]
Keywords: TP53, CD58, mutation, copy number loss, DLBCL
Received: September 24, 2015 Accepted: September 02, 2016 Published: November 4, 2016
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.
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