Genetic subtype classification using a simplified algorithm and mutational characteristics of diffuse large B-cell lymphoma in a Japanese cohort.

Abstract

Recent large-scale genetic studies have proposed a new genetic classification of diffuse large B-cell lymphoma (DLBCL), which is clinically and biologically heterogeneous. However, the classification methods were complicated to be introduced into clinical practice. Here we retrospectively evaluated the mutational status and copy number changes of 144 genes in 177 Japanese patients with DLBCL, using targeted DNA sequencing. We developed a simplified algorithm for classifying four genetic subtypes-MYD88, NOTCH2, BCL2, and SGK1-by assessing alterations in 18 representative genes and BCL2 and BCL6 rearrangement status, integrating the significant genes from previous studies. In our cohort and another validation cohort from published data, the classification results in our algorithm showed close agreement with the other established algorithm. A differential prognosis among the four groups was observed. The NOTCH2 group showed a particularly poorer outcome than similar groups in previous reports. Furthermore, our study revealed unreported genetic features in the DLBCL subtypes that are mainly reported in Japanese patients, such as CD5-positive DLBCL and methotrexate-associated lymphoproliferative disorders. These results indicate the utility of our simplified method for DLBCL genetic subtype classification, which can facilitate the optimisation of treatment strategies. In addition, our study highlights the genetic features of Japanese patients with DLBCL.

• Authors: Tatsuzo Mishina, Nagisa Oshima-Hasegawa, Shokichi Tsukamoto, Masaki Fukuyo, Hajime Kageyama, Tomoya Muto, Naoya Mimura, Bahityar Rahmutulla, Yurie Nagai, Kensuke Kayamori, Yutaro Hino, Shio Mitsukawa, Yusuke Takeda, Chikako Ohwada, Masahiro Takeuchi, Hideki Tsujimura, Tohru Iseki, Chiaki Nakaseko, Jun-Ichiro Ikeda, Makiko Itami, Koutaro Yokote, Osamu Ohara, Atsushi Kaneda, Emiko Sakaida
• Journal: British journal of haematology (Br J Haematol) Vol. 195 Issue 5 Pg. 731-742 (12 2021) ISSN: 1365-2141 [Electronic] England
• PMID: 34378195 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 British Society for Haematology and John Wiley & Sons Ltd.

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Algorithms
• Asian People (genetics)
• Cohort Studies
• DNA Mutational Analysis
• Female
• Humans
• Japan (epidemiology)
• Lymphoma, Large B-Cell, Diffuse (classification, epidemiology, genetics)
• Male
• Middle Aged
• Mutation
• Sequence Analysis, DNA
• Young Adult