%0 Journal Article
%T Genetic evidence implies that primary and relapsed tumors arise from common precursor cells in primary central nervous system lymphoma
%A Akira Matsumura
%A Eiichi Ishikawa
%A Hidekazu Nishikii
%A Keiichiro Hattori
%A Mamiko SakataŠ\Yanagimoto
%A Manabu Kusakabe
%A Masafumi Muratani
%A Masayuki Noguchi
%A Naoki Kurita
%A Naoshi Obara
%A Ryota Matsuoka
%A Shigeru Chiba
%A Shingo Takano
%A Takayasu Kato
%A Toru Nanmoku
%A Yasuhisa Yokoyama
%A Yasuhito Suehara
%A Yuichi Hasegawa
%J Archive of "Cancer Science".
%D 2019
%R 10.1111/cas.13848
%X Primary central nervous system lymphoma (PCNSL) is a rare subtype of lymphoma that arises within the brain or the eyes. PCNSL recurs within the central nervous system (CNS) in most relapsed cases, whereas extraŠ\CNS relapse is experienced in rare cases. The present study aimed at identifying the presence of common precursor cells (CPC) for primary intraŠ\ and relapsed extraŠ\CNS tumors, and further assessing the initiating events in bone marrow (BM). Targeted deep sequencing was carried out for five paired primary intraŠ\ and relapsed extraŠ\CNS tumors of PCNSL. Two to five mutations were shared by each pair of intraŠ\ and extraŠ\CNS tumors. In particular, MYD88 mutations, L265P in three and P258L in one, were shared by four pairs. Unique somatic mutations were observed in all five intraŠ\CNS tumors and in four out of five extraŠ\CNS tumors. Remarkably, IgH clones in the intraŠ\ and the extraŠ\CNS tumors in two pairs were distinct from each other, whereas one pair of tumors shared identical monoclonal IgH rearrangement. In a cohort of 23 PCNSL patients, L265P MYD88 mutations were examined in tumorŠ\free BM mononuclear cells (MNC) in which the PCNSL tumors had L265P MYD88 mutations. L265P MYD88 mutations were detected by a droplet digital PCR method in nine out of 23 bone marrow mononuclear cells. These results suggest that intraŠ\ and extraŠ\tumors are derived from CPC with MYD88 mutations in most PCNSL, arising either before or after IgH rearrangement. The initiating MYD88 mutations may occur during BŠ\cell differentiation in BM
%K bone marrow
%K common precursor cell
%K IgH rearrangement
%K L265P MYD88
%K primary central nervous system lymphoma
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317941/