Yingying Ye1, Ning Ding1, Lan Mi1, Yunfei Shi2, Weiping Liu1, Yuqin Song1, Shaokun Shu3, Jun Zhu4. 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Haidian District, No 52, Fucheng Road, Beijing, 100142, China. 2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Haidian District, No 52, Fucheng Road, Beijing, 100142, China. 3. Department of Biomedical Engineering, Peking University, Beijing, 100871, China. shaokun_shu@bjmu.edu.cn. 4. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Haidian District, No 52, Fucheng Road, Beijing, 100142, China. zhu-jun2017@outlook.com.
Abstract
OBJECTIVE: To explore the correlation of mutation landscape with clinical outcomes in patients with peripheral T-cell lymphoma (PTCL). METHODS: We retrospectively analyzed the clinicopathological and prognosis data of 53 patients with PTCL from November 2011 to December 2017. Targeted next-generation sequencing of a 659-gene panel was performed for tissues from 53 patients with PTCLs. The correlation of mutation landscape with clinical outcomes was analyzed. RESULTS: TET2 was the most frequently mutated gene (64%), followed by RHOA (43%), PCLO (23%), DNMT3A (19%), IDH2 (17%), PIEZO1 (17%) and TP53 (15%). When mutated genes were categorized into functional groups, the most common mutations were those involved in epigenetic/chromatin modification (75%), T-cell activation (74%), and the DNA repair/TP53 pathway (64%). TET2/TP53 mutations were significantly associated with positive B symptoms (P = 0.045), and elevated lactate dehydrogenase (LDH) level (P = 0.011). Moreover, TET2/TP53 mutation was a risk factor for PTCL patient survival (HR 3.574, 95% CI 1.069 - 11.941, P = 0.039). The occurrence of JAK/STAT pathway mutations in angioimmunoblastic T-cell lymphoma (AITL) patients conferred a worse progression-free survival (HR 2.366, 95% CI 0.9130-6.129, P = 0.0334). CONCLUSIONS: Heterogeneous gene mutations occur in PTCL, some of which have a negative impact on the survival outcome.
OBJECTIVE: To explore the correlation of mutation landscape with clinical outcomes in patients with peripheral T-cell lymphoma (PTCL). METHODS: We retrospectively analyzed the clinicopathological and prognosis data of 53 patients with PTCL from November 2011 to December 2017. Targeted next-generation sequencing of a 659-gene panel was performed for tissues from 53 patients with PTCLs. The correlation of mutation landscape with clinical outcomes was analyzed. RESULTS:TET2 was the most frequently mutated gene (64%), followed by RHOA (43%), PCLO (23%), DNMT3A (19%), IDH2 (17%), PIEZO1 (17%) and TP53 (15%). When mutated genes were categorized into functional groups, the most common mutations were those involved in epigenetic/chromatin modification (75%), T-cell activation (74%), and the DNA repair/TP53 pathway (64%). TET2/TP53 mutations were significantly associated with positive B symptoms (P = 0.045), and elevated lactate dehydrogenase (LDH) level (P = 0.011). Moreover, TET2/TP53 mutation was a risk factor for PTCL patient survival (HR 3.574, 95% CI 1.069 - 11.941, P = 0.039). The occurrence of JAK/STAT pathway mutations in angioimmunoblastic T-cell lymphoma (AITL) patients conferred a worse progression-free survival (HR 2.366, 95% CI 0.9130-6.129, P = 0.0334). CONCLUSIONS: Heterogeneous gene mutations occur in PTCL, some of which have a negative impact on the survival outcome.
Entities:
Keywords:
Peripheral T-cell lymphomas; Prognosis; Protein 53; Ten-eleven translocation 2
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