Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma
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 diagno...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
June 8, 2018
|
| In: |
Blood
Year: 2018, Volume: 132, Issue: 6, Pages: 587-597 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood-2018-03-840132 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1182/blood-2018-03-840132
|
| Author Notes: | Brian A. Walker, Konstantinos Mavrommatis, Christopher P. Wardell, T. Cody Ashby, Michael Bauer, Faith E. Davies, Adam Rosenthal, Hongwei Wang, Pingping Qu, Antje Hoering, Mehmet Samur, Fadi Towfic, Maria Ortiz, Erin Flynt, Zhinuan Yu, Zhihong Yang, Dan Rozelle, John Obenauer, Matthew Trotter, Daniel Auclair, Jonathan Keats, Niccolo Bolli, Mariateresa Fulciniti, Raphael Szalat, Philippe Moreau, Brian Durie, A. Keith Stewart, Hartmut Goldschmidt, Marc S. Raab, Hermann Einsele, Pieter Sonneveld, Jesus San Miguel, Sagar Lonial, Graham H. Jackson, Kenneth C. Anderson, Herve Avet-Loiseau, Nikhil Munshi, Anjan Thakurta, and Gareth J. Morgan |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1663620490 | ||
| 003 | DE-627 | ||
| 005 | 20220816141730.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 190425s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1182/blood-2018-03-840132 |2 doi | |
| 035 | |a (DE-627)1663620490 | ||
| 035 | |a (DE-599)KXP1663620490 | ||
| 035 | |a (OCoLC)1341211668 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Walker, Brian A. |e VerfasserIn |0 (DE-588)1184512817 |0 (DE-627)1663621322 |4 aut | |
| 245 | 1 | 0 | |a Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma |c Brian A. Walker, Konstantinos Mavrommatis, Christopher P. Wardell, T. Cody Ashby, Michael Bauer, Faith E. Davies, Adam Rosenthal, Hongwei Wang, Pingping Qu, Antje Hoering, Mehmet Samur, Fadi Towfic, Maria Ortiz, Erin Flynt, Zhinuan Yu, Zhihong Yang, Dan Rozelle, John Obenauer, Matthew Trotter, Daniel Auclair, Jonathan Keats, Niccolo Bolli, Mariateresa Fulciniti, Raphael Szalat, Philippe Moreau, Brian Durie, A. Keith Stewart, Hartmut Goldschmidt, Marc S. Raab, Hermann Einsele, Pieter Sonneveld, Jesus San Miguel, Sagar Lonial, Graham H. Jackson, Kenneth C. Anderson, Herve Avet-Loiseau, Nikhil Munshi, Anjan Thakurta, and Gareth J. Morgan |
| 264 | 1 | |c June 8, 2018 | |
| 300 | |a 11 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 25.04.2019 | ||
| 500 | |a This article has an Erratum 132(13):1461 | ||
| 520 | |a 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. | ||
| 700 | 1 | |a Goldschmidt, Hartmut |d 1956- |e VerfasserIn |0 (DE-588)102258023X |0 (DE-627)717003809 |0 (DE-576)365637386 |4 aut | |
| 700 | 1 | |a Raab, Marc-Steffen |d 1973- |e VerfasserIn |0 (DE-588)124052460 |0 (DE-627)706520998 |0 (DE-576)293998027 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Blood |d Washington, DC : American Society of Hematology, 1946 |g 132(2018), 6, Seite 587-597 |h Online-Ressource |w (DE-627)266886647 |w (DE-600)1468538-3 |w (DE-576)075961938 |x 1528-0020 |7 nnas |a Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma |
| 773 | 1 | 8 | |g volume:132 |g year:2018 |g number:6 |g pages:587-597 |g extent:11 |a Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1182/blood-2018-03-840132 |x Verlag |x Resolving-System |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20190425 | ||
| 993 | |a Article | ||
| 994 | |a 2018 | ||
| 998 | |g 124052460 |a Raab, Marc-Steffen |m 124052460:Raab, Marc-Steffen |d 910000 |d 910100 |e 910000PR124052460 |e 910100PR124052460 |k 0/910000/ |k 1/910000/910100/ |p 29 | ||
| 998 | |g 102258023X |a Goldschmidt, Hartmut |m 102258023X:Goldschmidt, Hartmut |d 910000 |d 910100 |e 910000PG102258023X |e 910100PG102258023X |k 0/910000/ |k 1/910000/910100/ |p 28 | ||
| 999 | |a KXP-PPN1663620490 |e 3453416732 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"person":[{"role":"aut","given":"Brian A.","family":"Walker","display":"Walker, Brian A."},{"role":"aut","given":"Hartmut","family":"Goldschmidt","display":"Goldschmidt, Hartmut"},{"given":"Marc-Steffen","role":"aut","display":"Raab, Marc-Steffen","family":"Raab"}],"id":{"doi":["10.1182/blood-2018-03-840132"],"eki":["1663620490"]},"type":{"bibl":"article-journal","media":"Online-Ressource"},"relHost":[{"recId":"266886647","language":["eng"],"note":["Gesehen am 21.04.2023"],"origin":[{"publisherPlace":"Washington, DC ; Philadelphia, Pa. ; Stanford, Calif.","dateIssuedKey":"1946","publisher":"American Society of Hematology ; Saunders ; HighWire Press","dateIssuedDisp":"1946-"}],"pubHistory":["1.1946 -"],"part":{"extent":"11","text":"132(2018), 6, Seite 587-597","volume":"132","year":"2018","pages":"587-597","issue":"6"},"disp":"Identification of novel mutational drivers reveals oncogene dependencies in multiple myelomaBlood","titleAlt":[{"title":"Blood online"}],"corporate":[{"role":"isb","display":"American Society of Hematology"}],"id":{"zdb":["1468538-3"],"issn":["1528-0020"],"eki":["266886647"]},"title":[{"title_sort":"Blood","title":"Blood","subtitle":"journal of the American Society of Hematology"}],"physDesc":[{"extent":"Online-Ressource"}],"type":{"bibl":"periodical","media":"Online-Ressource"}}],"title":[{"title":"Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma","title_sort":"Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma"}],"physDesc":[{"extent":"11 S."}],"note":["Gesehen am 25.04.2019","This article has an Erratum 132(13):1461"],"recId":"1663620490","language":["eng"],"origin":[{"dateIssuedKey":"2018","dateIssuedDisp":"June 8, 2018"}],"name":{"displayForm":["Brian A. Walker, Konstantinos Mavrommatis, Christopher P. Wardell, T. Cody Ashby, Michael Bauer, Faith E. Davies, Adam Rosenthal, Hongwei Wang, Pingping Qu, Antje Hoering, Mehmet Samur, Fadi Towfic, Maria Ortiz, Erin Flynt, Zhinuan Yu, Zhihong Yang, Dan Rozelle, John Obenauer, Matthew Trotter, Daniel Auclair, Jonathan Keats, Niccolo Bolli, Mariateresa Fulciniti, Raphael Szalat, Philippe Moreau, Brian Durie, A. Keith Stewart, Hartmut Goldschmidt, Marc S. Raab, Hermann Einsele, Pieter Sonneveld, Jesus San Miguel, Sagar Lonial, Graham H. Jackson, Kenneth C. Anderson, Herve Avet-Loiseau, Nikhil Munshi, Anjan Thakurta, and Gareth J. Morgan"]}} | ||
| SRT | |a WALKERBRIAIDENTIFICA8201 | ||