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Clinical Implications of Genomic Loss of Heterozygosity in Endometrial Carcinoma.
- Source :
-
JCO precision oncology [JCO Precis Oncol] 2021 Jun 15; Vol. 5. Date of Electronic Publication: 2021 Jun 15 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- Purpose: Homologous recombination deficiency, identified by homologous recombination deficiency gene alterations or high percentage of genome-wide loss of heterozygosity (gLOH), is associated with improved prognosis, platinum sensitivity (PS), and poly (ADP-ribose) polymerase inhibitor response in high-grade ovarian cancer. Since the copy number-high (CN-H) endometrial cancer molecular subtype (EC-MS) shares molecular features with high-grade ovarian cancer, our aim was to assign EC-MS on the basis of comprehensive genomic profiling (CGP) results and evaluate the gLOH status with clinical behavior of EC.<br />Methods: Eighty-two epithelial EC tumor tissues were sequenced by hybrid capture-based CGP, and results were used to assign EC-MS (ultramutated, microsatellite instability-high, CN-low; CN-high). Retrospective chart review established clinical characteristics, including PS. Relationships of PS, EC-MS, gene alterations, and gLOH were assessed statistically.<br />Results: PS and EC-MS of CN-H showed statistically significant difference in overall survival (OS). Most notably, when the CN-H EC-MS was subcategorized by gLOH status, there was a significant difference in OS with gLOH-H being associated with longer survival. Cox semi-proportional hazard modeling showed that gLOH, stage, and race were significant in modeling OS.<br />Conclusion: The method of assigning EC-MS by CGP demonstrates similar clinical features to previous reports of EC-MS assigned by other methods. CGP can also assess gLOH status with gLOH-H most commonly seen in CN-H tumors. CN-H, gLOH-H patients showed significantly improved OS (hazard ratio, 0.100 [0.02-0.51 95% CI]). Thus, gLOH status may be a meaningful prognostic biomarker within the CN-H tumors and possibly across EC-MS.<br />Competing Interests: Doug I. Lin Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Pharma AG Natalie Danziger Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Dean C. Pavlick Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Julia A. Elvin Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Marina Frimer Research Funding: GlaxoSmithKline No other potential conflicts of interest were reported. Doug I. Lin Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Pharma AG Natalie Danziger Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Dean C. Pavlick Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Julia A. Elvin Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Marina Frimer Research Funding: GlaxoSmithKline No other potential conflicts of interest were reported.<br /> (© 2021 by American Society of Clinical Oncology.)
Details
- Language :
- English
- ISSN :
- 2473-4284
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- JCO precision oncology
- Publication Type :
- Academic Journal
- Accession number :
- 34585039
- Full Text :
- https://doi.org/10.1200/PO.20.00393