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Molecular diagnostics of a single drug-resistant multiple myeloma case using targeted next-generation sequencing

Authors Ikeda H, Ishiguro K, Igarashi T, Aoki Y, Hayashi T, Ishida T, Sasaki Y, Tokino T, Shinomura Y

Received 13 April 2015

Accepted for publication 17 August 2015

Published 5 October 2015 Volume 2015:8 Pages 2805—2815

DOI https://doi.org/10.2147/OTT.S86515

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Professor Da Li

Peer reviewer comments 3

Editor who approved publication: Professor Daniele Santini


Hiroshi Ikeda,1 Kazuya Ishiguro,1 Tetsuyuki Igarashi,1 Yuka Aoki,1 Toshiaki Hayashi,1 Tadao Ishida,1 Yasushi Sasaki,1,2 Takashi Tokino,2 Yasuhisa Shinomura1

1Department of Gastroenterology, Rheumatology and Clinical Immunology, 2Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan

Abstract: A 69-year-old man was diagnosed with IgG λ-type multiple myeloma (MM), Stage II in October 2010. He was treated with one cycle of high-dose dexamethasone. After three cycles of bortezomib, the patient exhibited slow elevations in the free light-chain levels and developed a significant new increase of serum M protein. Bone marrow cytogenetic analysis revealed a complex karyotype characteristic of malignant plasma cells. To better understand the molecular pathogenesis of this patient, we sequenced for mutations in the entire coding regions of 409 cancer-related genes using a semiconductor-based sequencing platform. Sequencing analysis revealed eight nonsynonymous somatic mutations in addition to several copy number variants, including CCND1 and RB1. These alterations may play roles in the pathobiology of this disease. This targeted next-generation sequencing can allow for the prediction of drug resistance and facilitate improvements in the treatment of MM patients.

Keywords: multiple myeloma, drug resistance, genome-wide sequencing, semiconductor sequencer, target therapy

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