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Blood Cancer J. 2015 Mar 20;5:e299. doi: 10.1038/bcj.2015.24.

BRAF V600E mutation in early-stage multiple myeloma: good response to broad acting drugs and no relation to prognosis.

Author information

1
1] KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway [2] Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
2
Department of Pathology and Medical Genetics, St Olavs Hospital, Trondheim, Norway.
3
1] Department of Pathology and Medical Genetics, St Olavs Hospital, Trondheim, Norway [2] Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
4
1] Bioinformatics Core Facility, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway [2] Norwegian Cancer Genomics Consortium, Norway.
5
Bioinformatics Core Facility, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
6
1] Norwegian Cancer Genomics Consortium, Norway [2] Department of Tumor Biology, Institute for Cancer Research, Radium Hospital, Oslo University Hospital, Oslo, Norway.
7
1] Norwegian Cancer Genomics Consortium, Norway [2] Department of Tumor Biology, Institute for Cancer Research, Radium Hospital, Oslo University Hospital, Oslo, Norway [3] Institute for Cancer Genetics and Informatics, Radium Hospital, Oslo University Hospital, Oslo, Norway [4] Biomedical Informatics group, Department of Informatics, University of Oslo, Oslo, Norway.
8
1] Norwegian Cancer Genomics Consortium, Norway [2] Department of Tumor Biology, Institute for Cancer Research, Radium Hospital, Oslo University Hospital, Oslo, Norway [3] Bioinformatics Core facility, Institute for Cancer Research, Radium Hospital, Oslo University Hospital, Oslo, Norway.
9
1] Norwegian Cancer Genomics Consortium, Norway [2] Department of Tumor Biology, Institute for Cancer Research, Radium Hospital, Oslo University Hospital, Oslo, Norway [3] Genomics Core facility, Institute for Cancer Research, Radium Hospital, Oslo University Hospital, Oslo, Norway.
10
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
11
Department of Oncology, St Olavs Hospital, Trondheim, Norway.
12
1] KG Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, Trondheim, Norway [2] Bioinformatics Core Facility, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway [3] Norwegian Cancer Genomics Consortium, Norway [4] Department of Hematology, St Olavs Hospital, Trondheim, Norway.

Abstract

In this study, we analyzed the prevalence and clone size of BRAF V600E mutation in 209 patients with multiple myeloma and related the results to clinical phenotype, response and survival. Biopsies were screened for BRAF V600E by allele-specific real-time PCR (AS-PCR). Positive results were confirmed by immunohistochemistry, Sanger sequencing and, in three patients from whom we had stored purified myeloma cells, whole-exome sequencing. Eleven patients (5.3%) were BRAF V600E mutation positive by AS-PCR and at least one other method. The fraction of mutated cells varied from 4 to 100%. BRAF V600E-positive patients had no characteristic clinical phenotype except for significantly higher levels of serum creatinine (125 versus 86 μmol/l) Seven of eleven patients responded with at least very good partial response to alkylators, immunomodulatory agents or proteasome inhibitors. Progression-free and overall survival were similar in patients with and without the mutation. By this integrated approach, we found that patients with BRAF V600E mutation responded very well to broad acting drugs and there was no relation to prognosis in early-stage myeloma. In particular, a large mutated cell fraction did not correlate with aggressive disease.

PMID:
25794135
PMCID:
PMC4382665
DOI:
10.1038/bcj.2015.24
[Indexed for MEDLINE]
Free PMC Article

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