Impact of tumor percentage on the assessment of homologous recombination deficiency score using a NGS 523 gene panel and a cytogenetic software in the evaluation of epithelial ovarian tumors

Autor: Janira Navarro Sanchez, Zan Halford, Jason Kar Shing Pon, Amy M. Woron, Keith Y. Terada, Koah Vierkoetter, Christopher A. Lum
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Oncology. 40:e17567-e17567
ISSN: 1527-7755
0732-183X
Popis: e17567 Background: Platinum-taxane chemotherapy and surgical debulking are the optimal treatment for patients with advanced ovarian cancer. While initial response rates are above 80%, tumor recurrence occurs in about 70 to 80% of patients. Cells with defects in homologous recombination repair (HRR) are susceptible to cell death induced by Poly (ADP-ribose) polymerase inhibitors (PARPi). These drugs are used to treat recurrent neoplasms that have BRCA1 or BRCA2 mutations or homologous recombination deficiency (HRD). Low tumor percentage in test samples, which is common in clinical practice, is often overlooked when addressing HRD tests. The goal of this study was to determine the optimal tumor content rate needed to detect HRD changes. Methods: A total of sixteen ovarian neoplasms were studied. These samples were sequenced using Illumina TSO500 NGS and interpreted using NxClinical software 6.1. In all cases, HRD scores were evaluated. A score of ≥42 was determined to be HR-deficient and a score < 42 was considered HR-proficient. We aimed to identify the optimal tumor percentage needed for detection of HRD alterations. HRD scores were calculated with tumor percentages of 70%, 60%, 40%, and 20%. Additionally, chemotherapy response scores (CRS) were available in 8 of 16 cases. We correlated the CRS with HRD scores. Results: In this project, visualization of a 523-gene cancer exome panel was shown to be 66.7% sensitive and 100% specific for detecting genomic scars (HRD score). 68.75% of cases showed low HRD score and 31.25% of cases showed a high HRD score. Next generation sequencing (NGS) results for most specimens are adequate with a tumor content rate of 70%. CRS1 cases were HR-proficient. For CRS2 and CRS3 we had mixed results. Conclusions: HRD correlates with platinum sensitivity in epithelial ovarian tumors, which has clinical significance as a predictor of sensitivity to PARPi. During treatment, tissue samples are obtained at different times points and sources, some at diagnosis/surgical debulking and some after neoadjuvant therapy. After neoadjuvant treatment, tumor volume is reduced. Cytology specimens are convenient for obtaining tumoral cells, but tumor volumes are usually small. Profiling tumors of low volume decrease the chances of detecting a patient’s eligibility for targeted maintenance. Our next steps will evaluate the performance of tissue microarrays using the Infinium CytoSNP-850K array compared to NGC cytogenomics at low tumor volumes.
Databáze: OpenAIRE
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