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

Blood Cancer Journal
E H RustadA Waage

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.

References

Jul 21, 2006·Leukemia·B G M DurieUNKNOWN International Myeloma Working Group
Nov 28, 2006·Biochimica Et Biophysica Acta·James A McCubreyRichard A Franklin
Oct 28, 2009·Nucleic Acids Research·Christian J A SigristNicolas Hulo
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Oct 19, 2010·Nucleic Acids Research·Simon A ForbesP Andrew Futreal
Feb 24, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Georgina V LongRichard F Kefford
Mar 25, 2011·Nature·Michael A ChapmanTodd R Golub
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Sep 9, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joan BladéRay Powles
Apr 14, 2012·Blood·Jonathan J KeatsP Leif Bergsagel
May 25, 2012·The New England Journal of Medicine·Sascha DietrichThorsten Zenz
Feb 2, 2013·The Lancet Oncology·Sekwon Jang, Michael B Atkins
Feb 12, 2013·Nature Biotechnology·Kristian CibulskisGad Getz
Feb 15, 2013·The New England Journal of Medicine·Michael H RosoveJohn A Glaspy
Mar 1, 2013·Journal of Biomolecular Screening·Kristine MisundAnders Sundan
Apr 25, 2013·Cancer Discovery·Mindaugas AndrulisMarc S Raab
Jun 5, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Solange PetersStefan Zimmermann
Jul 17, 2013·The British Journal of Dermatology·H EkedahlG Jönsson
Oct 15, 2013·Nature Methods·Malachi GriffithRichard K Wilson
Nov 21, 2013·Nucleic Acids Research·UNKNOWN UniProt Consortium
Nov 30, 2013·Nucleic Acids Research·Robert D FinnMarco Punta
Jan 22, 2014·Clinical Lymphoma, Myeloma & Leukemia·Olga L BohnJulie Teruya-Feldstein
Jul 7, 2014·Clinical Lymphoma, Myeloma & Leukemia·J P SharmanS M Ali

❮ Previous
Next ❯

Citations

Apr 14, 2016·Journal of Oncology Practice·Sagar Lonial, Ajay K Nooka
Mar 8, 2018·Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG·Maria Rita GaiserJochen Sven Utikal
Sep 23, 2016·Clinical Journal of the American Society of Nephrology : CJASN·Rimda WanchooKenar D Jhaveri
Jul 22, 2019·Journal of Clinical Medicine·Antonio Giovanni SolimandoHermann Einsele
Jun 2, 2016·American Society of Clinical Oncology Educational Book·Ajay K Nooka, Sagar Lonial
Jan 29, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eileen M BoyleBrian A Walker
Jan 14, 2021·Cancers·Teru Hideshima, Kenneth C Anderson
Jan 1, 2021·Case Reports in Hematology·Steve Biko OtienoRobert Johnson
May 18, 2021·Rare Tumors·Muhamad Alhaj MoustafaHan W Tun
Jan 13, 2018·Chemical Reviews·Alicia J AngelbelloMatthew D Disney

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsies
biopsy
PCR
exome sequencing
ISS

Software Mentioned

IndelRealigner
CASAVA
PFAM
COSMIC
Picard FixMateInformation
PROSITE
GATK RealignerTargetCreator
Infinity analyze
GATK BaseRecalibrator
ANNOVAR

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.