An in-house testing for detection of homologous recombination repair deficiency (HRD) in patients with solid tumors.

Authors

null

Shuguang Tan

Department of Gastrointestinal Surgery, Hengyang Central Hospital, Hengyang, China

Shuguang Tan , Weifeng Guo , Bin Cai , Tianhao Mu , Ming Liu , Zhouyang Wang , Yanqing Zhou , Yan Yin

Organizations

Department of Gastrointestinal Surgery, Hengyang Central Hospital, Hengyang, China, Quanzhou First Hospital.Fujian, Quanzhou, China, Department of Anesthesiology,Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China, HaploX Biotechnology Co., Ltd., Shenzhen, China, HaploX Biotechnology, Shenzhen, China

Research Funding

No funding received
None.

Background: HRD is associated with sensitivity towards PARP inhibitors (PARPi) in various cancer types, such as ovarian cancer, breast cancer, pancreatic cancer, and prostate cancer, and its determination is used as a biomarker for therapy decision making. HRD leads to the larger genome alterations, called “genomic scars“, which comprise loss of heterozygosity (LOH), telomeric allelic imbalance (TAI) and large scale state transitions(LST). The detection of SNPs is capable of measuring chromosomal abnormalities including genomic scars as mentioned above. Methods: Using a panel targeting more than 50,000 SNPs that evenly spaced across the entire human genome and the next generation sequencing technique, we developed an in-house testing for HRD detection, namely HRD score, which was computed by combining the measurements of large genomic defects including LOH, TAI, and LST. Then, we detected 44 ovarian cancer patients without BRCA1/2 mutations and 14 ovarian cancer patients harboring BRCA1/2 mutations to explore the application possibility of HRD score 42 as the threshold for HRD patients. Furthermore, we studied the HRD score distribution of 494 solid tumor patients. Results: For the 44 ovarian cancer patients without BRCA mutation, 50% (22/44) of them had the HRD score greater than 42. For the 14 ovarian cancer patients harboring BRCA1/2 mutations, 100%(14/14) of them had the HRD score greater than 42. For the 494 solid tumor patients, 38.66% (191/494) of them had the HRD score greater than 42. Conclusions: For this in-house HRD testing, the percentage of ovarian cancer patients without BRCA mutation who had HRD score greater than 42 was consistent with former report. Besides, the HRD score of all the 14 ovarian cancer patients harboring BRCA1/2 mutations were greater than 42, which was consistent with the facts. Therefore, it seems applicable to define the patients with HRD score greater than 42 as HRD positive. In addition, there is a wide range of demands for comprehensive implementation of HRD testing for other tumor entities.

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Publication Only: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Track

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Sub Track

Circulating Biomarkers

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr e15025)

DOI

10.1200/JCO.2023.41.16_suppl.e15025

Abstract #

e15025

Abstract Disclosures

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