Genetic heterogeneity and prognostic impact of recurrent ANK2 and TP53 mutations in mantle cell lymphoma: a multi-centre cohort study

• Published in: Scientific reports Vol. 10; no. 1; p. 13359
• Main Authors: Jeong, Seri, Park, Yu Jin, Yun, Woobin, Lee, Seung-Tae, Choi, Jong Rak, Suh, Cheolwon, Jo, Jae-Cheol, Cha, Hee Jeong, Jeong, Jee-Yeong, Chang, HeeKyung, Cha, Yoon Jin, Kim, Hyerim, Park, Min-Jeong, Song, Wonkeun, Cho, Eun-Hae, Jeong, Eun-Goo, Lee, Junnam, Park, Yongmin, Lee, Yong Seok, Kim, Da Jung, Lee, Ho Sup
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.08.2020; Nature Publishing Group
• Subjects: 631/67/1990; 631/67/68; 692/4017; Aged; Ankyrins - genetics; Apoptosis; Cell cycle; Cell death; Cohort analysis; Female; Gene expression; Genetic Heterogeneity; Genetic Predisposition to Disease - genetics; Humanities and Social Sciences; Humans; Kaplan-Meier Estimate; Lymphoma; Lymphoma, Mantle-Cell - diagnosis; Lymphoma, Mantle-Cell - genetics; Lymphoma, Mantle-Cell - mortality; Male; Mantle cell lymphoma; Middle Aged; multidisciplinary; Multivariate analysis; Mutation; Mutation - genetics; p53 Protein; Population studies; Prognosis; Progression-Free Survival; Republic of Korea - epidemiology; Science; Science (multidisciplinary); Survival Analysis; Tumor Suppressor Protein p53 - genetics; Whole Genome Sequencing; Republic of Korea
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-70310-9

The molecular features of mantle cell lymphoma (MCL), including its increased incidence, and complex therapies have not been investigated in detail, particularly in East Asian populations. In this study, we performed targeted panel sequencing (TPS) and whole-exome sequencing (WES) to investigate the genetic alterations in Korean MCL patients. We obtained a total of 53 samples from MCL patients from five Korean university hospitals between 2009 and 2016. We identified the recurrently mutated genes such as SYNE1 , ATM , KMT2D , CARD11 , ANK2 , KMT2C , and TP53 , which included some known drivers of MCL. The mutational profiles of our cohort indicated genetic heterogeneity. The significantly enriched pathways were mainly involved in gene expression, cell cycle, and programmed cell death. Multivariate analysis revealed that ANK2 mutations impacted the unfavourable overall survival (hazard ratio [HR] 3.126; P  = 0.032). Furthermore, TP53 mutations were related to worse progression-free survival (HR 7.813; P  = 0.043). Among the recurrently mutated genes with more than 15.0% frequency, discrepancies were found in only 5 genes from 4 patients, suggesting comparability of the TPS to WES in practical laboratory settings. We provide the unbiased genetic landscape that might contribute to MCL pathogenesis and recurrent genes conferring unfavourable outcomes.