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000142199 0247_ $$2ISSN$$a1079-6533
000142199 0247_ $$2ISSN$$a1528-0020
000142199 0247_ $$2ISSN$$a1938-1336
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000142199 037__ $$aDKFZ-2019-00013
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000142199 1001_ $$00000-0002-8615-6254$$aWalker, Brian A$$b0
000142199 245__ $$aIdentification of novel mutational drivers reveals oncogene dependencies in multiple myeloma.
000142199 260__ $$aStanford, Calif.$$bHighWire Press$$c2018
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000142199 520__ $$aUnderstanding the profile of oncogene and tumor suppressor gene mutations with their interactions and impact on the prognosis of multiple myeloma (MM) can improve the definition of disease subsets and identify pathways important in disease pathobiology. Using integrated genomics of 1273 newly diagnosed patients with MM, we identified 63 driver genes, some of which are novel, including IDH1, IDH2, HUWE1, KLHL6, and PTPN11 Oncogene mutations are significantly more clonal than tumor suppressor mutations, indicating they may exert a bigger selective pressure. Patients with more driver gene abnormalities are associated with worse outcomes, as are identified mechanisms of genomic instability. Oncogenic dependencies were identified between mutations in driver genes, common regions of copy number change, and primary translocation and hyperdiploidy events. These dependencies included associations with t(4;14) and mutations in FGFR3, DIS3, and PRKD2; t(11;14) with mutations in CCND1 and IRF4; t(14;16) with mutations in MAF, BRAF, DIS3, and ATM; and hyperdiploidy with gain 11q, mutations in FAM46C, and MYC rearrangements. These associations indicate that the genomic landscape of myeloma is predetermined by the primary events upon which further dependencies are built, giving rise to a nonrandom accumulation of genetic hits. Understanding these dependencies may elucidate potential evolutionary patterns and lead to better treatment regimens.
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000142199 7001_ $$aMavrommatis, Konstantinos$$b1
000142199 7001_ $$00000-0002-9416-7818$$aWardell, Christopher P$$b2
000142199 7001_ $$aAshby, T Cody$$b3
000142199 7001_ $$aBauer, Michael$$b4
000142199 7001_ $$aDavies, Faith E$$b5
000142199 7001_ $$aRosenthal, Adam$$b6
000142199 7001_ $$aWang, Hongwei$$b7
000142199 7001_ $$aQu, Pingping$$b8
000142199 7001_ $$aHoering, Antje$$b9
000142199 7001_ $$aSamur, Mehmet$$b10
000142199 7001_ $$aTowfic, Fadi$$b11
000142199 7001_ $$aOrtiz, Maria$$b12
000142199 7001_ $$aFlynt, Erin$$b13
000142199 7001_ $$aYu, Zhinuan$$b14
000142199 7001_ $$aYang, Zhihong$$b15
000142199 7001_ $$aRozelle, Dan$$b16
000142199 7001_ $$aObenauer, John$$b17
000142199 7001_ $$aTrotter, Matthew$$b18
000142199 7001_ $$aAuclair, Daniel$$b19
000142199 7001_ $$aKeats, Jonathan$$b20
000142199 7001_ $$aBolli, Niccolo$$b21
000142199 7001_ $$aFulciniti, Mariateresa$$b22
000142199 7001_ $$aSzalat, Raphael$$b23
000142199 7001_ $$aMoreau, Philippe$$b24
000142199 7001_ $$aDurie, Brian$$b25
000142199 7001_ $$aStewart, A Keith$$b26
000142199 7001_ $$aGoldschmidt, Hartmut$$b27
000142199 7001_ $$0P:(DE-He78)1cb537e833afd985097ccfaddffb2ef3$$aRaab, Marc-Steffen$$b28$$udkfz
000142199 7001_ $$aEinsele, Hermann$$b29
000142199 7001_ $$aSonneveld, Pieter$$b30
000142199 7001_ $$aSan Miguel, Jesus$$b31
000142199 7001_ $$aLonial, Sagar$$b32
000142199 7001_ $$aJackson, Graham H$$b33
000142199 7001_ $$aAnderson, Kenneth C$$b34
000142199 7001_ $$aAvet-Loiseau, Herve$$b35
000142199 7001_ $$aMunshi, Nikhil$$b36
000142199 7001_ $$aThakurta, Anjan$$b37
000142199 7001_ $$aMorgan, Gareth J$$b38
000142199 773__ $$0PERI:(DE-600)1468538-3$$a10.1182/blood-2018-03-840132$$gVol. 132, no. 6, p. blood-2018-03-840132 -$$n6$$p587-597$$tBlood$$v132$$x0006-4971$$y2018
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