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Challenges in next generation sequencing of homology recombination repair genomic variants in prostate cancer: A nationwide survey and calibration project in China

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机构: [1]Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. [2]Department of Urology, Peking University First Hospital, Beijing 100034, China. [3]Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China. [4]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. [5]Institute of Pathology, Fudan University, Shanghai 200032, China. [6]Department of Urology, West China Hospital Sichuan University, Chengdu 610041, China. [7]Cellular & Molecular Diagnostics Center, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510288, China. [8]Department of Molecular Diagnostic, Sun Yat-sen University Cancer Center, Guangzhou 510700, China. [9]Department of Urology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510630, China.
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关键词: prostate cancer homologous recombination repair gene testing next-generation sequencing national questionnaire survey external quality assessment

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Homologous Recombination Repair (HRR) is the most reliable and important signaling pathway for repairing DNA damage. We initiated a calibration project to better understand the NGS landscape for HRR gene testing in China, provide indications for testing standardization, and guide clinical practice.A questionnaire was used to collect laboratory information, panel design for HRR gene testing, tissue sample test parameters, plasma ctDNA sample test parameters, and procedures for variant interpretation. The testing quality of the participating laboratories was further evaluated by external quality assessment (EQA), which provided 5 FFPE slices and 5 mimic ctDNA samples as standard references for evaluation. Test results and reports were collected to assess laboratory performance.Our results showed that different laboratories had significant differences in sequencing platforms, library construction technologies, genes in the testing panel, detectable mutation types, probe coverage regions, sequencing parameters, variants interpretation guidelines, and positive test rates. For the EQA test, the overall pass rate was about 60%. The average accuracy for tissue samples and ctDNA samples was 79.55% and 74.13%, respectively. It is worth noting that variants in tandem repetition regions and splice sites, and those with low allele frequency were more prone to misdetection. The most common reasons for misdetection were as follows: the testing panel did not cover the genes or the whole exon and splice sites of the genes; the variants were misclassified as benign or likely benign, and the variants failed the QC criteria.The discrepancies observed in our survey and EQA test affect the authenticity of HRR gene test results for prostate cancer, underlining the need to establish guidelines for HRR gene testing and variant interpretation in China, and to optimize HRR gene testing in clinical practice to improve management and patient care.© 2022 Asian Pacific Prostate Society. Publishing services by Elsevier B.V.

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大类 | 4 区 医学
小类 | 4 区 泌尿学与肾脏学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 泌尿学与肾脏学
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Q2 UROLOGY & NEPHROLOGY
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Q2 UROLOGY & NEPHROLOGY

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第一作者机构: [1]Department of Pathology, State Key Laboratory of Complex Severe and Rare Diseases, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
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