Genetic evidence implies that primary and relapsed tumors arise from common precursor cells in primary central nervous system lymphoma

It was suggested that primary intra ‐central nervous system (CNS) tumors and relapsed extra‐CNS tumors are derived from common precursor cells with MYD88 mutations in most primary CNS lymphomas. The initiating MYD88 mutations may occur during B‐cell differentiation in BM. 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 extra ‐CNS relapse is experienced in rare cases. The present study aimed at identifying the presence of common precursor cells (CPC) for primary intra‐ and relapsed extra‐CNS tumors, and further assessing the initiating events in bone marrow (BM). Targeted deep sequencing was carried out for five pa ired primary intra‐ and relapsed extra‐CNS tumors of PCNSL. Two to five mutations were shared by each pair of intra‐ and extra‐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 intra ‐CNS tumors and in four out of five extra‐CNS tumors. Remarkably,IgH clones in the intra ‐ and the extra‐CNS tumors in two pairs were distinct from each other, whereas one pair of tumors shared identical monoclonalIgH rearrangement. In a cohort of 23 PCNSL patients, L265PMYD88 mutations were examined in tumor ‐free BM mononuclear cells (MNC) in which the PCNSL tumors had L265PMYD88 mutations. L265PMYD...

Source: Cancer Science - November 18, 2018 Category: Cancer & Oncology Authors: Keiichiro Hattori, Mamiko Sakata ‐Yanagimoto, Manabu Kusakabe, Toru Nanmoku, Yasuhito Suehara, Ryota Matsuoka, Masayuki Noguchi, Yasuhisa Yokoyama, Takayasu Kato, Naoki Kurita, Hidekazu Nishikii, Naoshi Obara, Shingo Takano, Eiichi Ishikawa Tags: ORIGINAL ARTICLE Source Type: research