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@ARTICLE{Walker:142199,
author = {B. A. Walker and K. Mavrommatis and C. P. Wardell and T. C.
Ashby and M. Bauer and F. E. Davies and A. Rosenthal and H.
Wang and P. Qu and A. Hoering and M. Samur and F. Towfic and
M. Ortiz and E. Flynt and Z. Yu and Z. Yang and D. Rozelle
and J. Obenauer and M. Trotter and D. Auclair and J. Keats
and N. Bolli and M. Fulciniti and R. Szalat and P. Moreau
and B. Durie and A. K. Stewart and H. Goldschmidt and M.-S.
Raab$^*$ and H. Einsele and P. Sonneveld and J. San Miguel
and S. Lonial and G. H. Jackson and K. C. Anderson and H.
Avet-Loiseau and N. Munshi and A. Thakurta and G. J. Morgan},
title = {{I}dentification of novel mutational drivers reveals
oncogene dependencies in multiple myeloma.},
journal = {Blood},
volume = {132},
number = {6},
issn = {0006-4971},
address = {Stanford, Calif.},
publisher = {HighWire Press},
reportid = {DKFZ-2019-00013},
pages = {587-597},
year = {2018},
abstract = {Understanding the profile of oncogene and tumor suppressor
gene mutations with their interactions and impact on the
prognosis of multiple myeloma (MM) can improve the
definition of disease subsets and identify pathways
important in disease pathobiology. Using integrated genomics
of 1273 newly diagnosed patients with MM, we identified 63
driver genes, some of which are novel, including IDH1, IDH2,
HUWE1, KLHL6, and PTPN11 Oncogene mutations are
significantly more clonal than tumor suppressor mutations,
indicating they may exert a bigger selective pressure.
Patients with more driver gene abnormalities are associated
with worse outcomes, as are identified mechanisms of genomic
instability. Oncogenic dependencies were identified between
mutations in driver genes, common regions of copy number
change, and primary translocation and hyperdiploidy events.
These dependencies included associations with t(4;14) and
mutations in FGFR3, DIS3, and PRKD2; t(11;14) with mutations
in CCND1 and IRF4; t(14;16) with mutations in MAF, BRAF,
DIS3, and ATM; and hyperdiploidy with gain 11q, mutations in
FAM46C, and MYC rearrangements. These associations indicate
that the genomic landscape of myeloma is predetermined by
the primary events upon which further dependencies are
built, giving rise to a nonrandom accumulation of genetic
hits. Understanding these dependencies may elucidate
potential evolutionary patterns and lead to better treatment
regimens.},
cin = {G170},
ddc = {610},
cid = {I:(DE-He78)G170-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29884741},
pmc = {pmc:PMC6097138},
doi = {10.1182/blood-2018-03-840132},
url = {https://inrepo02.dkfz.de/record/142199},
}