Analysis of MDM2 Amplification: Next-Generation Sequencing of Patients With Diverse Malignancies

JCO Precision Oncology
Shumei KatoRazelle Kurzrock

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

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Citations

Nov 22, 2019·The Oncologist·Jacob J AdashekRazelle Kurzrock
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
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

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Software Mentioned

Genomics Evidence Neoplasia Information Exchange ( GENIE )
Genomics Evidence Neoplasia Information Exchange ( GENIE
GraphPad
GENIE
GraphPad Prism

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