Molecular diagnostics of a single drug-resistant multiple myeloma case using targeted next-generation sequencing.
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.
Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University, Sapporo, Japan.
Hiroshi
H
Ikeda
Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University, Sapporo, Japan.
Kazuya
K
Ishiguro
Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University, Sapporo, Japan.
Tetsuyuki
T
Igarashi
Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University, Sapporo, Japan.
Yuka
Y
Aoki
Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University, Sapporo, Japan.
Toshiaki
T
Hayashi
Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University, Sapporo, Japan.
Tadao
T
Ishida
Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University, Sapporo, Japan ; Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
Yasushi
Y
Sasaki
Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan.
Takashi
T
Tokino
Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University, Sapporo, Japan.
Yasuhisa
Y
Shinomura
drug resistance; genome-wide sequencing; multiple myeloma; semiconductor sequencer; target therapy