In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 2 ( 2021-2-5), p. e0246322-
Abstract:
To investigate the prognostic value of gene variants and copy number variations (CNVs) in patients with newly diagnosed multiple myeloma (NDMM), an integrative genomic analysis was performed. Methods Sixty-seven patients with NDMM exhibiting more than 60% plasma cells in the bone marrow aspirate were enrolled in the study. Whole-exome sequencing was conducted on bone marrow nucleated cells. Mutation and CNV analyses were performed using the CNVkit and Nexus Copy Number software. In addition, karyotype and fluorescent in situ hybridization were utilized for the integrated analysis. Results Eighty-three driver gene mutations were detected in 63 patients with NDMM. The median number of mutations per patient was 2.0 (95% confidence interval [CI] = 2.0–3.0, range = 0–8). MAML2 and BHLHE41 mutations were associated with decreased survival. CNVs were detected in 56 patients (72.7%; 56/67). The median number of CNVs per patient was 6.0 (95% CI = 5.7–7.0; range = 0–16). Among the CNVs, 1q gain, 6p gain, 6q loss, 8p loss, and 13q loss were associated with decreased survival. Additionally, 1q gain and 6p gain were independent adverse prognostic factors. Increased numbers of CNVs and driver gene mutations were associated with poor clinical outcomes. Cluster analysis revealed that patients with the highest number of driver mutations along with 1q gain, 6p gain, and 13q loss exhibited the poorest prognosis. Conclusions In addition to the known prognostic factors, the integrated analysis of genetic variations and CNVs could contribute to prognostic stratification of patients with NDMM.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0246322
DOI:
10.1371/journal.pone.0246322.g001
DOI:
10.1371/journal.pone.0246322.g002
DOI:
10.1371/journal.pone.0246322.g003
DOI:
10.1371/journal.pone.0246322.g004
DOI:
10.1371/journal.pone.0246322.g005
DOI:
10.1371/journal.pone.0246322.g006
DOI:
10.1371/journal.pone.0246322.g007
DOI:
10.1371/journal.pone.0246322.g008
DOI:
10.1371/journal.pone.0246322.g009
DOI:
10.1371/journal.pone.0246322.t001
DOI:
10.1371/journal.pone.0246322.t002
DOI:
10.1371/journal.pone.0246322.t003
DOI:
10.1371/journal.pone.0246322.t004
DOI:
10.1371/journal.pone.0246322.s001
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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