GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE65777 Query DataSets for GSE65777
Status Public on Nov 23, 2016
Title A Genome Wide Association Study Reveals Genetic Predisposition for Bortezomib-Induced Peripheral Neuropathy in Multiple Myeloma by Variation in the PREP1-CBS locus.
Organism Homo sapiens
Experiment type SNP genotyping by SNP array
Genome variation profiling by SNP array
Summary We performed a genome-wide association study using Affymetrix HD-SNP arrays 6.0 to identify risk variants for developing bortezomib-induced peripheral neuropathy (BiPN) in 469 multiple myeloma (MM) patients who received bortezomib-dexamethasone (VD) induction therapy prior to autologous stem-cell transplantation (ASCT) and conducted validation in an independent cohort of 114 MM patients. We identified one previously unreported gene locus associated with BiPN at 21q22.3 (rs2839629, PKNOX1; OR = 1.89, P= 6.47 x 10-7). PKNOX1 is known to regulate expression of MCP-1, a potent mediator of chemotherapy-induced peripheral neuropathy. rs2839629 is in strong linkage disequilibrium (LD, r2 = 0.87) with rs915854, localized 6.5kb centromeric to CBS encoding an endogenous H2S-producing enzyme. CBS-H2S signalling pathway is implicated in the pathogenesis of a variety of neurodegenerative and inflammatory disorders, and specifically in neuropathy models. Our data provide conclusive evidence for genetic susceptibility to BiPN in MM and new potential targets in neuro-protective strategies of treatment.
Overall design Identify risk variants for developing bortezomib-induced peripheral neuropathy (BiPN) within a cohort of 469 MM patients by means of genome wide association study, validation in an independent cohort of 114 MM patients
Contributor(s) Magrangeas F, Kuiper R, Avet-Loiseau H, Gouraud W, Guérin-Charbonnel C, Aussem A, Elghazel H, Suhard J, Der Sakissian H, Attal M, Sonneveld P, Dumontet C, Moreau P, van Duin M, Campion L, Minvielle S
Citation(s) 27060151
Submission date Feb 09, 2015
Last update date Nov 27, 2018
Contact name Wilfried Gouraud
Organization name ICO - UMGC
Department Integrated Center of Oncology René Gauducheau
Lab Omics Data Science Unit
Street address bd Jacques Monod
City Saint Herblain
ZIP/Postal code 44805
Country France
Platforms (1)
GPL6801 [GenomeWideSNP_6] Affymetrix Genome-Wide Human SNP 6.0 Array
Samples (469)
GSM1604271 IFM_001
GSM1604272 IFM_002
GSM1604273 IFM_003
BioProject PRJNA275004

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE65777_RAW.tar 13.9 Gb (http)(custom) TAR (of CEL)
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap