TY  - JOUR
A1  - Keppler, Sarah
A1  - Weißbach, Susann
A1  - Langer, Christian
A1  - Knop, Stefan
A1  - Pischimarov, Jordan
A1  - Kull, Miriam
A1  - Stühmer, Thorsten
A1  - Steinbrunn, Torsten
A1  - Bargou, Ralf
A1  - Einsele, Hermann
A1  - Rosenwald, Andreas
A1  - Leich, Ellen
T1  - Rare SNPs in receptor tyrosine kinases are negative outcome predictors in multiple myeloma
JF  - Oncotarget
N2  - Multiple myeloma (MM) is a plasma cell disorder that is characterized by a great genetic heterogeneity. Recent next generation sequencing studies revealed an accumulation of tumor-associated mutations in receptor tyrosine kinases (RTKs) which may also contribute to the activation of survival pathways in MM. To investigate the clinical role of RTK-mutations in MM, we deep-sequenced the coding DNA-sequence of EGFR, EPHA2, ERBB3, IGF1R, NTRK1 and NTRK2 which were previously found to be mutated in MM, in 75 uniformly treated MM patients of the “Deutsche Studiengruppe Multiples Myelom”. Subsequently, we correlated the detected mutations with common cytogenetic alterations and clinical parameters. We identified 11 novel non-synonymous SNVs or rare patient-specific SNPs, not listed in the SNP databases 1000 genomes and dbSNP, in 10 primary MM cases. The mutations predominantly affected the tyrosine-kinase and ligand-binding domains and no correlation with cytogenetic parameters was found. Interestingly, however, patients with RTK-mutations, specifically those with rare patient-specific SNPs, showed a significantly lower overall, event-free and progression-free survival. This indicates that RTK SNVs and rare patient-specific RTK SNPs are of prognostic relevance and suggests that MM patients with RTK-mutations could potentially profit from treatment with RTK-inhibitors.
KW  - multiple myeloma
KW  - rare SNP
KW  - amplicon sequencing
KW  - receptor tyrosine kinases
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177840
VL  - 7
IS  - 25
ER  -