Abstract
MDM2 amplification can promote tumorigenesis directly or indirectly through p53 inhibition. MDM2 has increasing clinical relevance because inhibitors are under evaluation in clinical trials, and MDM2 amplification is a possible genomic correlate of accelerated progression, known as hyperprogression, after anti-PD-1/PD-L1 immunotherapy. We used next-generation sequencing (NGS) to ascertain MDM2 amplification status across a large number of diverse cancers. We interrogated the molecular profiles of 102,878 patients with diverse malignancies for MDM2 amplification and co-altered genes using clinical-grade NGS (182 to 465 genes). MDM2 amplification occurred in 3.5% of patients (3,650 of 102,878). The majority of tumor types had a small subset of patients with MDM2 amplification. Most of these patients (99.0% [3,613/3,650]) had co-alterations that accompanied MDM2 amplification. Various pathways, including those related to tyrosine kinase (37.9% [1,385 of 3,650]), PI3K signaling (25.4% [926 of 3,650]), TP53 (24.9% [910 of 3,650]), and MAPK signaling (23.6% [863 of 3,650]), were involved. Although infrequent, mismatch repair genes and PD-L1 amplification also were co-altered (2.2% [79 of 3,650]). Most patients (97.6% [3,563 of 3,650]...Continue Reading
References
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·S N JonesA Bradley
Feb 4, 2003·Nature Reviews. Cancer·Patrick Chène
Jun 27, 2006·Nature Medicine·Roman K ThomasMatthew Meyerson
Sep 6, 2008·Nature·UNKNOWN Cancer Genome Atlas Research Network
Dec 17, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Moriko ItoJoanna Lisztwan
Oct 12, 2011·Molecular and Cellular Biology·Sheng ZhouMuxiang Zhou
May 16, 2012·Cancer Discovery·Nikhil WagleLevi A Garraway
Sep 12, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Apostolia-Maria TsimberidouRazelle Kurzrock
Dec 25, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Qin Li, Guillermina Lozano
Jan 11, 2013·Nature Reviews. Cancer·Mark WadeGeoffrey M Wahl
May 15, 2013·Oncotarget·Rabin SaidRazelle Kurzrock
Oct 22, 2013·Nature Biotechnology·Garrett M FramptonRoman Yelensky
Dec 9, 2014·The New England Journal of Medicine·Stephen M AnsellPhilippe Armand
Feb 13, 2015·Cancer Research·Maria SchwaederléRazelle Kurzrock
Feb 20, 2015·Molecular Cancer Therapeutics·Sandip Pravin Patel, Razelle Kurzrock
Mar 25, 2015·Oncotarget·Marta KovatchevaAndrew Koff
Jun 2, 2015·The New England Journal of Medicine·Dung T LeLuis A Diaz
Aug 26, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Maria SchwaederleRazelle Kurzrock
Sep 12, 2015·Critical Reviews in Oncology/hematology·Loredana UrsoGiulia Pasello
Sep 18, 2015·Journal of the National Cancer Institute·Denis L JardimRazelle Kurzrock
Oct 23, 2015·Cell Death & Disease·E S Kim, J M Shohet
Dec 10, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·K KoehlerJ L Chen
Mar 12, 2016·Blood·Jie HeRoss L Levine
Jan 1, 2015·Cell Death Discovery·A LakomaE S Kim
Jun 9, 2016·JAMA Oncology·Maria SchwaederleRazelle Kurzrock
Jun 30, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Philippe ArmandCraig H Moskowitz
Jul 29, 2016·Molecular Cancer Therapeutics·Jennifer J WhelerRazelle Kurzrock
Oct 26, 2016·BMC Medicine·Jason RoszikScott E Woodman
Nov 9, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Stéphane ChampiatCharles Ferté
Feb 28, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Andrew J WagnerDavid S Hong
Mar 23, 2017·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Maja de JongeJan H M Schellens
Mar 30, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shumei KatoRazelle Kurzrock
Apr 19, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E Saâda-BouzidC Le Tourneau
Apr 20, 2017·Genome Medicine·Zachary R ChalmersGarrett M Frampton
Jun 3, 2017·Cancer Discovery·UNKNOWN AACR Project GENIE Consortium
Jun 21, 2017·Cancer Discovery·Kent W MouwAlan D D'Andrea
Aug 25, 2017·Molecular Cancer Therapeutics·Aaron M GoodmanRazelle Kurzrock
Citations
Nov 22, 2019·The Oncologist·Jacob J AdashekRazelle Kurzrock
Mar 1, 2020·Cancers·Andrea ForschnerTobias Sinnberg
Nov 17, 2019·Virchows Archiv : an International Journal of Pathology·Jera JerucEmanuela Boštjančič
Apr 9, 2020·Frontiers in Immunology·Morgane DenisCharles Dumontet
Aug 28, 2020·Frontiers in Oncology·Rilan BaiJiuwei Cui
Mar 3, 2020·Oncoimmunology·Shumei KatoRazelle Kurzrock
Oct 1, 2020·Clinical and Translational Medicine·Xue-Jiao HanXia-Wei Wei
Feb 12, 2020·The Oncologist·Jacob J AdashekRazelle Kurzrock
Apr 4, 2021·Diagnostics·Raf Sciot
Apr 21, 2021·Clinical Lung Cancer·Luis Cabezón-GutiérrezParham Khosravi-Shahi
Aug 10, 2021·Frontiers in Immunology·Shuyue WangTengfei Liu