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Cocktail & Poster Display session

87P - Clinical features and genetic profile of MDM2-altered solid tumors


06 Mar 2023


Cocktail & Poster Display session


Julia Tejerina-Peces


Annals of Oncology (2023) 8 (1suppl_2): 100898-100898. 10.1016/esmoop/esmoop100898


J. Tejerina-Peces1, J. Bartolomé Arcilla1, M. De La Hoya1, P. Garre1, M. Paz Cabezas1, A. López de Sá1, S. Cabezas-Camarero1, B. García Paredes1, N. Vidal Cassinello1, C. Aguado1, G. Marquina Ospina1, G. Fernandez-Hinojal2, A. Orta1, L. Ortega3, A. Ocana Fernandez1, P. Pérez Segura1, A. Manzano Fernández1

Author affiliations

  • 1 Medical Oncology Department, Hospital Clinico Universitario San Carlos, 28040 - Madrid/ES
  • 2 Medical Oncology Department, Clinica Universidad de Navarra, Madrid/ES
  • 3 Pathology, Hospital Clinico Universitario San Carlos, 28040 - Madrid/ES


This content is available to ESMO members and event participants.

Abstract 87P


MDM2 is a negative regulator of p53 that directly inhibits the transcriptional activation of p53 targeting its ubiquitination and degradation by the proteasome. In addition, MDM2 has a p53-independent effect by modulating other molecular pathways involved in cell growth, proliferation and death. Information about the accompanying genetic co-alterations in MDM2-altered tumors, including its relationship with the immune system and other oncogenic pathways, is scarce. New agents targeting MDM2 are currently under development. A better knowledge of the clinical and molecular features of MDM2-altered tumors is needed to establish the treatment for these tumors.


We performed an observational retrospective study at Hospital Clínico San Carlos (Madrid, Spain) in 816 advanced solid tumor patients undergoing Next Generation Sequencing (NGS) on tumor samples (n=807) or liquid biopsies (n=9) between July 2019 and December 2022. Clinical data, tumor mutational burden (TMB) and accompanying genetic alterations of the MDM2-altered tumors were recorded (n= 33, 4%).


Of the 33 MDM2-altered tumors, we found 26 (79%) amplifications (2 of them with co-existing MDM2 rearrangements) and 7 (21%) non-previously described frameshift mutations. The most frequent tumors were liposarcoma (n=8, 24%), lung cancer (n=7; 21%) and head and neck cancer (n=4; 12%). Most common accompanying genetic alterations were related to cell cycle (TP53 and/or CDK4, 88%), DNA repair pathway (BRCA2, ATRX, ATM, RAD54L and/or POLE, 52%) and chromatin modulation pathway (BRD4, MLL2 and/or SMARCA4, 30%). There were 7 TMB-high (cut-off > 10 mpm) tumors (3.78-174) in 2 melanoma, 2 lung cancer, 1 breast cancer, 1 parotid cancer and 1 cancer of unknown primary. 5 of them related to mutations in MDM2. There was only one microsatellite instability (MSI) in a patient with TMB-high breast tumor.


In our cohort, solid tumors with MDM2 alterations had accompanying genetic alterations affecting chromatin modulation and DNA repair pathway. MDM2 mutated solid tumors presented a trend to high TMB. These findings could help to develop new combination strategies for MDM2-altered tumors with immunotherapy or chromatin or DNA repair targeted agents.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

J. Tejerina-Peces, Hospital Clínico San Carlos.


Has not received any funding.


All authors have declared no conflicts of interest.

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