1. The clonal evolution during long-term clinical course of multiple myeloma
- Author
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Norihito Inoue, Noriko Nishimura, Yasuhito Terui, Takashi Okabe, Yuji Mishima, Yuko Mishima, Masahiro Yokoyama, Hideki Uryu, Takanori Fukuta, Yuko Shirouchi, and Kiyohiko Hatake
- Subjects
Oncology ,medicine.medical_specialty ,Somatic cell ,Disease ,Gene mutation ,Somatic evolution in cancer ,Clonal Evolution ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Databases, Genetic ,Biomarkers, Tumor ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Gene ,Multiple myeloma ,Aged ,Neoplasm Staging ,Hematology ,business.industry ,Computational Biology ,Genetic Variation ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Cell Transformation, Neoplastic ,Treatment Outcome ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Mutation ,Disease Progression ,Female ,Disease Susceptibility ,Bone marrow ,Multiple Myeloma ,business ,Follow-Up Studies ,030215 immunology - Abstract
Somatic gene mutations related to acceleration disease and clonal evolution in multiple myeloma strongly influence severe clinical outcomes. In this study, we traced the transition of somatic mutations during the clinical course of myeloma patients over a long-term follow-up period (8.5 year average). Seven myeloma cases treated with immuno-chemotherapy at our institution were analyzed with clinical courses and the results of FISH and G-band analyses. Furthermore, the target sequences in regard to 121 genes, related to driver mutations or acceleration of disease in myeloma, were performed using bone marrow myeloma samples by next-generation sequencing, Ion Proton™ System. We detected a relationship between an increase in the dominant mutated gene (e.g., TP53, DIS3, FAM46C, KDM6B, and EGR1) and poor prognosis. In particular, clonal escalation of the TP53 mutation could not be overcome by any treatment. The selection of a combination treatment conducted in conjunction with the monitoring of gene mutations is appropriate for long-term survival. Our data demonstrate that long-term follow-up of somatic gene mutations during the clinical course of myeloma is helpful in the development of an effective treatment strategy.
- Published
- 2020
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