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Cancer Research and Treatment
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Cancer Research and Treatment
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Clinical Impact of Somatic Variants in Homologous Recombination Repair-Related Genes in Ovarian High-Grade Serous Carcinoma

Authors: Chan Lee; Sohyun Hwang; Tae-Heon Kim; Hyun Soo Park; Haeyoun Kang; Min Chul Choi; Sang Geun Jung; +4 Authors

Clinical Impact of Somatic Variants in Homologous Recombination Repair-Related Genes in Ovarian High-Grade Serous Carcinoma

Abstract

PurposeIn this study, we investigated the frequencies of mutations in DNA damage repair genes including <i>BRCA1</i>, <i>BRCA2</i>, homologous recombination genes and <i>TP53</i> gene in ovarian high-grade serous carcinoma, alongside those of germline and somatic <i>BRCA</i> mutations, with the aim of improving the identification of patients suitable for treatment with poly(ADP-ribose) polymerase inhibitors.Materials and MethodsTissue samples from 77 Korean patients with ovarian high-grade serous carcinoma were subjected to next-generation sequencing. Pathogenic alterations of 38 DNA damage repair genes and <i>TP53</i> gene and their relationships with patient survival were examined. Additionally, we analyzed <i>BRCA</i> germline variants in blood samples from 47 of the patients for comparison.Results<i>BRCA1</i>, <i>BRCA2</i>, and <i>TP53</i> mutations were detected in 28.6%, 5.2%, and 80.5% of the 77 patients, respectively. Alterations in <i>RAD50, ATR, MSH6, MSH2</i>, and <i>FANCA</i> were also identified. At least one mutation in a DNA damage repair gene was detected in 40.3% of patients (31/77). Germline and somatic <i>BRCA</i> mutations were found in 20 of 47 patients (42.6%), and four patients had only somatic mutations without germline mutations (8.5%, 4/47). Patients with DNA damage repair gene alterations with or without <i>TP53</i>mutation, exhibited better disease-free survival than those with <i>TP53</i> mutation alone.ConclusionDNA damage repair genes were mutated in 40.3% of patients with high-grade serous carcinoma, with somatic <i>BRCA</i> mutations in the absence of germline mutation in 8.5%. Somatic variant examination, along with germline testing of DNA damage repair genes, has potential to detect additional candidates for PARP inhibitor treatment.

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Keywords

Adult, Aged, 80 and over, Ovarian Neoplasms, Recombinational DNA Repair, Middle Aged, Cystadenocarcinoma, Serous, Humans, Original Article, Female, Aged

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
16
Top 10%
Average
Top 10%
Green
gold