Comparative genetic analysis of central nervous system lymphomas between sites in the central nervous system or extracranial organs

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08950
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Kyorin University
• Principal Investigator: Kobayashi Keiichi 杏林大学, 医学部, 学内講師 (70406990)
• Co-Investigator(Kenkyū-buntansha): 市村 幸一 国立研究開発法人国立がん研究センター, 研究所, 分野長 (40231146) ; 永根 基雄 杏林大学, 医学部, 教授 (60327468)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 中枢神経系悪性リンパ腫 / 二次性中枢神経系悪性リンパ腫 / 遺伝子変異解析

Outline of Final Research Achievements

In order to search for mutations of central nervous system (CNS) lymphomas which might serve as driver mutations in the CNS, we have performed targeted sequencing in paired samples from four secondary central nervous system lymphoma (SCNSL) cases and two systemic relapse of primary central nervous system (PCNSL) cases. Mutational profiles were compared between the primary and recurrent tumor. MYD88, CD79B and PIM1 mutations were observed as shared mutations in all cases, therefore seemed to be relatively early genetic events. In the SCNSL cases, several de novo mutations were enriched only among the recurrent CNS tumors. One of those mutations were observed in 3/4 (75%) cases, and two mutations were observed in 2/4 (50%) cases. It is suggested that these de novo mutations in the recurrent CNS tumors might serve as driver mutations in the CNS. Further analysis in larger cohorts, and functional studies are required in order to validate these findings.

Free Research Field

悪性脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

PCNSL全身性再発、SCNSLに関する遺伝学的解析はその希少性から、特にPCNSL全身性再発、SCNSLの両者を解析し比較検討した報告は少ない。今回複数の遺伝子異常がDLBCLの中枢神経系病変に特徴的であることが示唆されたことはPCNSL、SCNSLの病態解明に寄与するとともに、予後不良であるこれらの疾患における治療標的としての検討につながる社会的意義がある。