Abstract
Clinically applicable platforms revealing actionable genomic alterations may improve the treatment efficacy of myeloma patients. In this pilot study, we used a high depth targeted sequencing panel containing 83 anti-cancer drug target genes to sequence genomic DNAs extracted from bone marrow aspirates of 23 patients with myeloma and 12 patients with amyloid light-chain (AL) amyloidosis. Mutation analysis revealed NRAS as the most commonly mutated gene (30%, 7/23) in myeloma patients followed by KRAS (26%, 6/23) and BRAF (22%, 5/23). However, no significant mutations were found in the 12 patients with AL amyloidosis. Notably, 6 of the 23 myeloma patients showed multi-site and/or multi-gene mutations in NRAS, KRAS, or BRAF, indicating compound aberrations in the Mitogen activated protein kinase (MAPK) pathway. Gene panel sequencing also revealed cytogenetic abnormalities associated with prognosis in myeloma patients. In conclusion, our pilot study suggests that targeted gene sequencing may have an important prognostic value for myeloma patients for the identification of actionable genomic alterations and cytogenetic aberrations.
Highlights
Since novel drugs such as proteasome inhibitors and immunomodulatory agents were first introduced for the treatment of multiple myeloma, survival outcomes have significantly improved [1,2,3]
Bortezomib-containing treatment was used for patients ineligible for autologous stem cell transplant (ASCT), whereas thalidomide-containing treatment was done for patients eligible for ASCT
No mutations were found in patients with amyloid light-chain (AL) amyloidosis alone, patients with myeloma combined with AL amyloidosis did show mutations in all three genes (Figure 1B)
Summary
Since novel drugs such as proteasome inhibitors and immunomodulatory agents were first introduced for the treatment of multiple myeloma, survival outcomes have significantly improved [1,2,3]. As treatment outcome may be associated with cytogenetic abnormalities at diagnosis, patients with multiple genetic alterations might show worse prognosis than patients without them [6, 7]. Patients with myeloma may have heterogeneous subclones, and the identification of genetic abnormalities with low frequency in these subclones could be helpful for a better understanding of each patient with myeloma. It www.impactjournals.com/oncotarget is difficult to detect low frequency genetic alterations in small subclones by conventional molecular testing using malignant plasma cells from bone marrow. The development of clinically applicable platforms revealing genomic alterations could help to improve a risk-adapted treatment strategy. We performed a pilot study to evaluate the feasibility of a targeted gene sequencing panel consisting of 83 genes in myeloma and AL amyloidosis patients
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