Development of molecular targeted therapy for primary central nervous system lymphomas

2015 Fiscal Year Final Research Report

• Project/Area Number: 24390347
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Ryuya YAMANAKA 京都府立医科大学, 医学部, 教授 (20323991)
• Co-Investigator(Kenkyū-buntansha): IKENAKA Kazuhiro 生理学研究所, 分子神経生理部門, 教授 (00144527) ; KAWAGUCHI Atsush 佐賀大学, 医学部, 教授 (60389319) ; HAYANO Azusa 京都府立医科大学, 医学研究科, 博士研究員 (10379018)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 脳リンパ腫 / ゲノム解析 / エクソーム解析 / 分子標的療法

Outline of Final Research Achievements

To delineate the genetic basis of PCNSL pathogenesis, we performed a comprehensive genetic study. We first analyzed paired tumor/normal DNA from 35 PCNSL cases by whole-exome sequencing (WES). Significantly mutated genes identified by WES and previously known mutational targets in PCNSL and systemic DLBCL were further screened for mutations using SureSelect-based targeted deep sequencing (Agilent) in an extended cohort of PCNSL cases (N = 90). Copy number alterations (CNAs) have been also investigated using SNP array-karyotyping (N =54).
WES, SNP array karyotyping and follow-up targeted sequencing of a large cohort of PCNSL cases revealed the genetic landscape of PCNSL, which were more homogeneous than that of systemic DLBCL, and thought to be involved in activation of constitutive NF-KB/TLR/BCR signaling, escape from immunosurveillance, as well as highly frequent SHMs.

Free Research Field

脳神経外科学、臨床腫瘍学