Details

Autor(en) / Beteiligte

• 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

Titel

Prevalence of MDM2 amplification and coalterations in 523 advanced cancer patients in the MD Anderson phase 1 clinic

Ist Teil von

• Oncotarget, 2018-09, Vol.9 (69), p.33232-33243

Ort / Verlag

United States: Impact Journals LLC

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 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. 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 amplification using FoundationOne's genomic profiling assay. Patients whose tumors expressed amplification were compared to those with tumors of the same histologic types without amplification. We tested tumors from 523 patients, of which 23 (4.4%) had amplification. The highest prevalence of 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 amplification was amplification (70%). mutation was also detected in 7 patients (30%). amplification was most commonly associated with liposarcoma. Concomitant alterations in additional genes such as amplification and mutations, along with variable responses to targeted therapies including MDM2 inhibitors, suggest that further combinational studies are needed to target this population.