Comprehensive genomic profiling of recurrent endometrial cancer: Implications for selection of systemic therapy
| Autor: | Annie Y. Liu, Julia A. Elvin, Nabilah Abdelaal, Jianyu Rao, Joshua G. Cohen, Jacquline N. Fahey, Xiaoyan Wang, Tiffany S. Lai, Laura L. Holman, E.N. Prendergast, Kathleen M. Moore, Gottfried E. Konecny, Maira P. Campos |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_treatment DNA Mutational Analysis Systemic therapy Targeted therapy 0302 clinical medicine Endometrial cancer 80 and over Comprehensive genomic profiling Cancer Aged 80 and over Obstetrics and Gynecology High-Throughput Nucleotide Sequencing Middle Aged Serous fluid Local 030220 oncology & carcinogenesis DNA mismatch repair Female Microsatellite Instability Biotechnology Adult medicine.medical_specialty Oncology and Carcinogenesis Article Paediatrics and Reproductive Medicine 03 medical and health sciences Internal medicine Next generation sequencing medicine Genetics Humans Oncology & Carcinogenesis Neoplasm Staging Retrospective Studies Aged business.industry Human Genome Microsatellite instability medicine.disease Endometrial Neoplasms Clinical trial 030104 developmental biology Neoplasm Recurrence Good Health and Well Being Neoplasm Recurrence Local business Clear cell |
| Zdroj: | Gynecologic oncology, vol 154, iss 3 |
| Popis: | Objectives To assess whether comprehensive genomic profiling (CGP) in the setting of routine clinical care allows molecular classification of recurrent endometrial cancer (EC) into the four Cancer Genome Atlas (TCGA) categories: POLE ultramutated, microsatellite instable, copy-number low, and copy-number high and whether this approach can identify genomic alterations (GAs) which inform treatment decisions. Methods Archival tissues from 74 patients diagnosed with recurrent EC were prospectively analyzed using hybrid-capture-based genomic profiling. Tumor mutational burden and microsatellite instability were measured. Clinically relevant GAs (CRGAs) were defined as GAs associated with targeted therapies available on-label or in mechanism-driven clinical trials. Results Using POLE mutational analysis, mismatch repair status, and p53 mutational analysis as surrogate for ‘copy-number’ status CGP segregated all cases into four TCGA molecular subgroups. While recurrent serous ECs were predominantly copy-number high, we found no clear prevalence of a specific molecular subtype in endometrioid, clear cell or undifferentiated tumors. Every tumor sample had at least one GA and 91% (67/74) had at least one CRGA. In this series 32% (24/74) of patients received a matched therapy based on the results of CGP. Objective responses to the matched therapy were seen in 25% (6/24) of patients with an additional 37.5% (9/24) achieving stable disease leading to a clinical benefit rate of 62.5% with a median treatment duration of 14.6 months (range 4.3–69 months). Conclusions CGP allows molecular classification of EC into four TCGA categories and allows identification of potential biomarkers for matched therapy in the setting of routine clinical care. |
| Databáze: | OpenAIRE |
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