Cargando…
Prevalence of MDM2 amplification and coalterations in 523 advanced cancer patients in the MD Anderson phase 1 clinic
BACKGROUND: TP53 is the most commonly mutated gene in cancer and codes for the best studied tumor suppressor, p53. MDM2 is involved in the negative regulation of p53 and itself serves as an oncogene, reported to be overexpressed in several cancer tumor types. In this retrospective study, we assessed...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145698/ https://www.ncbi.nlm.nih.gov/pubmed/30237864 http://dx.doi.org/10.18632/oncotarget.26075 |
_version_ | 1783356294389825536 |
---|---|
author | Dembla, Vikas Somaiah, Neeta Barata, Pedro Hess, Kenneth Fu, Siqing Janku, Filip Karp, Daniel D. Naing, Aung Piha-Paul, Sarina Anne Subbiah, Vivek Tsimberidou, Apostolia M. Shaw, Kenna Meric-Bernstam, Funda Hong, David S. |
author_facet | Dembla, Vikas Somaiah, Neeta Barata, Pedro Hess, Kenneth Fu, Siqing Janku, Filip Karp, Daniel D. Naing, Aung Piha-Paul, Sarina Anne Subbiah, Vivek Tsimberidou, Apostolia M. Shaw, Kenna Meric-Bernstam, Funda Hong, David S. |
author_sort | Dembla, Vikas |
collection | PubMed |
description | BACKGROUND: TP53 is the most commonly mutated gene in cancer and codes for the best studied tumor suppressor, p53. MDM2 is involved in the negative regulation of p53 and itself serves as an oncogene, reported to be overexpressed in several cancer tumor types. In this retrospective study, we assessed the occurrence of MDM2 amplification among patients with various types of cancers and its association with clinical factors, other genetic aberrations, and response to targeted therapy in a phase I clinical trial setting. METHODS: Samples from patients with advanced solid tumors who had been referred to the MD Anderson phase I clinical trials program between January 2011 and January 2016 were collected and analyzed for MDM2 amplification using FoundationOne’s genomic profiling assay. Patients whose tumors expressed MDM2 amplification were compared to those with tumors of the same histologic types without MDM2 amplification. RESULTS: We tested tumors from 523 patients, of which 23 (4.4%) had MDM2 amplification. The highest prevalence of MDM2 amplification was in sarcoma (57%), breast cancer (13%) and bladder cancer (9%). Six patients with liposarcoma were treated on phase I protocol with an MDM2 inhibitor. The most common molecular aberrations co-occurring with MDM2 amplification was CDK4 amplification (70%). TP53 mutation was also detected in 7 patients (30%). CONCLUSION: MDM2 amplification was most commonly associated with liposarcoma. Concomitant alterations in additional genes such as CDK4 amplification and TP53 mutations, along with variable responses to targeted therapies including MDM2 inhibitors, suggest that further combinational studies are needed to target this population. |
format | Online Article Text |
id | pubmed-6145698 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-61456982018-09-20 Prevalence of MDM2 amplification and coalterations in 523 advanced cancer patients in the MD Anderson phase 1 clinic Dembla, Vikas Somaiah, Neeta Barata, Pedro Hess, Kenneth Fu, Siqing Janku, Filip Karp, Daniel D. Naing, Aung Piha-Paul, Sarina Anne Subbiah, Vivek Tsimberidou, Apostolia M. Shaw, Kenna Meric-Bernstam, Funda Hong, David S. Oncotarget Research Paper BACKGROUND: TP53 is the most commonly mutated gene in cancer and codes for the best studied tumor suppressor, p53. MDM2 is involved in the negative regulation of p53 and itself serves as an oncogene, reported to be overexpressed in several cancer tumor types. In this retrospective study, we assessed the occurrence of MDM2 amplification among patients with various types of cancers and its association with clinical factors, other genetic aberrations, and response to targeted therapy in a phase I clinical trial setting. METHODS: Samples from patients with advanced solid tumors who had been referred to the MD Anderson phase I clinical trials program between January 2011 and January 2016 were collected and analyzed for MDM2 amplification using FoundationOne’s genomic profiling assay. Patients whose tumors expressed MDM2 amplification were compared to those with tumors of the same histologic types without MDM2 amplification. RESULTS: We tested tumors from 523 patients, of which 23 (4.4%) had MDM2 amplification. The highest prevalence of MDM2 amplification was in sarcoma (57%), breast cancer (13%) and bladder cancer (9%). Six patients with liposarcoma were treated on phase I protocol with an MDM2 inhibitor. The most common molecular aberrations co-occurring with MDM2 amplification was CDK4 amplification (70%). TP53 mutation was also detected in 7 patients (30%). CONCLUSION: MDM2 amplification was most commonly associated with liposarcoma. Concomitant alterations in additional genes such as CDK4 amplification and TP53 mutations, along with variable responses to targeted therapies including MDM2 inhibitors, suggest that further combinational studies are needed to target this population. Impact Journals LLC 2018-09-04 /pmc/articles/PMC6145698/ /pubmed/30237864 http://dx.doi.org/10.18632/oncotarget.26075 Text en Copyright: © 2018 Dembla et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Dembla, Vikas Somaiah, Neeta Barata, Pedro Hess, Kenneth Fu, Siqing Janku, Filip Karp, Daniel D. Naing, Aung Piha-Paul, Sarina Anne Subbiah, Vivek Tsimberidou, Apostolia M. Shaw, Kenna Meric-Bernstam, Funda Hong, David S. Prevalence of MDM2 amplification and coalterations in 523 advanced cancer patients in the MD Anderson phase 1 clinic |
title | Prevalence of MDM2 amplification and coalterations in 523 advanced cancer patients in the MD Anderson phase 1 clinic |
title_full | Prevalence of MDM2 amplification and coalterations in 523 advanced cancer patients in the MD Anderson phase 1 clinic |
title_fullStr | Prevalence of MDM2 amplification and coalterations in 523 advanced cancer patients in the MD Anderson phase 1 clinic |
title_full_unstemmed | Prevalence of MDM2 amplification and coalterations in 523 advanced cancer patients in the MD Anderson phase 1 clinic |
title_short | Prevalence of MDM2 amplification and coalterations in 523 advanced cancer patients in the MD Anderson phase 1 clinic |
title_sort | prevalence of mdm2 amplification and coalterations in 523 advanced cancer patients in the md anderson phase 1 clinic |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145698/ https://www.ncbi.nlm.nih.gov/pubmed/30237864 http://dx.doi.org/10.18632/oncotarget.26075 |
work_keys_str_mv | AT demblavikas prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic AT somaiahneeta prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic AT baratapedro prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic AT hesskenneth prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic AT fusiqing prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic AT jankufilip prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic AT karpdanield prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic AT naingaung prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic AT pihapaulsarinaanne prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic AT subbiahvivek prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic AT tsimberidouapostoliam prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic AT shawkenna prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic AT mericbernstamfunda prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic AT hongdavids prevalenceofmdm2amplificationandcoalterationsin523advancedcancerpatientsinthemdandersonphase1clinic |