Department of Laboratory Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 07441, South Korea.
Department of Laboratory Medicine, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 03722, South Korea.
Sci Rep. 2020 Aug 7;10(1):13359. 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.
套细胞淋巴瘤（Mantle Cell Lymphoma，MCL）的分子特征，包括其发病率的增加和复杂的治疗方法，尚未得到详细研究，特别是在东亚人群中。在这项研究中，我们进行了靶向panel 测序（Targeted Panel Sequencing，TPS）和全外显子组测序（Whole-Exome Sequencing，WES），以研究韩国 MCL 患者的遗传改变。我们从 2009 年至 2016 年期间，从五所韩国大学医院的 MCL 患者中总共获得了 53 个样本。我们鉴定了重复突变的基因，如 SYNE1、ATM、KMT2D、CARD11、ANK2、KMT2C 和 TP53，其中包括一些已知的 MCL 驱动基因。我们队列的突变谱表明存在遗传异质性。显著富集的途径主要涉及基因表达、细胞周期和程序性细胞死亡。多变量分析显示，ANK2 突变影响不良的总生存期（风险比 [HR] 3.126；P=0.032）。此外，TP53 突变与更差的无进展生存期相关（HR 7.813；P=0.043）。在反复突变的基因中，频率高于 15.0%的基因中，只有 4 名患者的 5 个基因存在差异，这表明在实际实验室环境中，TPS 与 WES 具有可比性。我们提供了无偏倚的遗传图谱，这可能有助于 MCL 的发病机制和导致不良结局的反复出现的基因。
