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Genomic analysis of multiple myeloma using targeted capture sequencing in the Japanese cohort |
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| Authors: | Takashi Kanamori Masashi Sanada Masaki Ri Hiroo Ueno Dai Nishijima Takahiko Yasuda Takuto Tachita Tomoko Narita Shigeru Kusumoto Atsushi Inagaki Rei Ishihara Yuki Murakami Nobuhiko Kobayashi Yusuke Shiozawa Kenichi Yoshida Masahiro M. Nakagawa Yasuhito Nannya Yuichi Shiraishi Kenichi Chiba Hiroko Tanaka Satoru Miyano Keizo Horibe Hiroshi Handa Seishi Ogawa Shinsuke Iida |
| Affiliation: | 1. Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Japan;2. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Japan;3. Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan;4. Department of Hematology and Oncology, Nagoya City West Medical Center, Japan;5. Department of Laboratory Science, Gunma University Graduate School of Health Science, Japan;6. Department of Hematology, Gunma University Graduate School of Medicine, Japan;7. Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Japan;8. Division of Cellular Signaling, National Cancer Center Research Institute, Japan;9. Human Genome Center, Institute of Medical Science, The University of Tokyo, Japan;10. Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Japan |
| Abstract: | Previous genomic studies have revealed the genomic landscape of myeloma cells. Although some of the genomic abnormalities shown are believed to be correlated to the molecular pathogenesis of multiple myeloma and/or clinical outcome, these correlations are not fully understood. The aim of this study is to elucidate the correlation between genomic abnormalities and clinical characteristics by targeted capture sequencing in the Japanese multiple myeloma cohort. We analysed 154 patients with newly diagnosed multiple myeloma. The analysis revealed that the study cohort consisted of a less frequent hyperdiploid subtype (37·0%) with relatively high frequencies of KRAS mutation (36·4%) and IGH-CCND1 translocation (26·6%) compared with previous reports. Moreover, our targeted capture sequencing strategy was able to detect rare IGH-associated chromosomal translocations, such as IGH-CCND2 and IGH-MAFA. Interestingly, all 10 patients harboured MAX mutations accompanied by 14q23 deletion. The patients with del(17p) exhibited an unfavourable clinical outcome, and the presence of KRAS mutation was associated with shorter survival in patients with multiple myeloma, harbouring IGH-CCND1. Thus, our study provides a detailed landscape of genomic abnormalities, which may have potential clinical application for patients with multiple myeloma. |
| Keywords: | next-generation sequencing multiple myeloma IGH-CCND2 IGH-MAFA racial difference |