Emily N Prendergast1, Laura L Holman2, Annie Y Liu1, Tiffany S Lai1, Maira P Campos3, Jacquline N Fahey1, Xiaoyan Wang4, Nabilah Abdelaal2, Jian Yu Rao5, Julia A Elvin6, Kathleen M Moore2, Gottfried E Konecny7, Joshua G Cohen1. 1. University of California Los Angeles, Division of Gynecologic Oncology, Los Angeles, CA, USA. 2. Stephenson Oklahoma Cancer Center, Division of Gynecologic Oncology, Oklahoma City, OK, USA. 3. University of California Los Angeles, Division of Hematologic Oncology, Los Angeles, CA, USA. 4. University of California Los Angeles, Division of General Medicine and Health Services Research, USA. 5. University of California Los Angeles, Department of Pathology, Los Angeles, CA, USA. 6. Foundation Medicine, Inc., 150 Second Street, Cambridge, MA, USA. 7. University of California Los Angeles, Division of Gynecologic Oncology, Los Angeles, CA, USA; University of California Los Angeles, Division of Hematologic Oncology, Los Angeles, CA, USA. Electronic address: gkonecny@mednet.ucla.edu.
Abstract
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.
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.
Authors: Eirwen M Miller; Nicole E Patterson; Gregory M Gressel; Rouzan G Karabakhtsian; Michal Bejerano-Sagie; Nivedita Ravi; Alexander Maslov; Wilber Quispe-Tintaya; Tao Wang; Juan Lin; Harriet O Smith; Gary L Goldberg; Dennis Y S Kuo; Cristina Montagna Journal: BMC Med Genomics Date: 2020-11-30 Impact factor: 3.063
Authors: Dora Čerina; Višnja Matković; Kristina Katić; Ingrid Belac Lovasić; Robert Šeparović; Ivana Canjko; Blanka Jakšić; Ana Fröbe; Stjepko Pleština; Žarko Bajić; Eduard Vrdoljak Journal: Pathol Oncol Res Date: 2021-09-27 Impact factor: 3.201