Utility of Homologous Recombination Deficiency Biomarkers Across Cancer Types
PURPOSE: Homologous recombination DNA repair deficiency (HRD) is associated with sensitivity to platinum and poly (ADP-ribose) polymerase inhibitors in certain cancer types, including breast, ovarian, pancreatic, and prostate. In these cancers, BRCA1/2 alterations and genomic scar signatures are useful indicators for assessing HRD. However, alterations in other homologous recombination repair (HRR)-related genes and their clinical significance in other cancer types have not been adequately and systematically investigated.
METHODS: We obtained data sets of all solid tumors in The Cancer Genome Atlas and comprehensively analyzed HRR pathway gene alterations, their loss-of-heterozygosity status, per-sample genomic scar scores, ie, the HRD score and mutational signature 3 ratio, DNA methylation profiles, gene expression profiles, somatic TP53 mutations, sex, and clinical information including chemotherapeutic regimens.
RESULTS: Biallelic alterations in HRR genes other than BRCA1/2 were also associated with elevated genomic scar scores. The association between HRR-related gene alterations and genomic scar scores differed significantly by sex and the presence of somatic TP53 mutations. HRD cases determined by a combination of these indices also showed HRD features in gene expression analysis and were associated with better survival when treated with DNA-damaging agents.
CONCLUSION: This study provides evidence for the usefulness of HRD analysis in all cancer types, improves chemotherapy decision making and its efficacy in clinical settings, and represents a substantial advancement in precision oncology.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
JCO precision oncology - 6(2022) vom: 04. Mai, Seite e2200085 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Takamatsu, Shiro [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarkers |
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| Anmerkungen: |
Date Completed 27.05.2022 Date Revised 27.08.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1200/PO.22.00085 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM341358150 |
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| 520 | |a PURPOSE: Homologous recombination DNA repair deficiency (HRD) is associated with sensitivity to platinum and poly (ADP-ribose) polymerase inhibitors in certain cancer types, including breast, ovarian, pancreatic, and prostate. In these cancers, BRCA1/2 alterations and genomic scar signatures are useful indicators for assessing HRD. However, alterations in other homologous recombination repair (HRR)-related genes and their clinical significance in other cancer types have not been adequately and systematically investigated | ||
| 520 | |a METHODS: We obtained data sets of all solid tumors in The Cancer Genome Atlas and comprehensively analyzed HRR pathway gene alterations, their loss-of-heterozygosity status, per-sample genomic scar scores, ie, the HRD score and mutational signature 3 ratio, DNA methylation profiles, gene expression profiles, somatic TP53 mutations, sex, and clinical information including chemotherapeutic regimens | ||
| 520 | |a RESULTS: Biallelic alterations in HRR genes other than BRCA1/2 were also associated with elevated genomic scar scores. The association between HRR-related gene alterations and genomic scar scores differed significantly by sex and the presence of somatic TP53 mutations. HRD cases determined by a combination of these indices also showed HRD features in gene expression analysis and were associated with better survival when treated with DNA-damaging agents | ||
| 520 | |a CONCLUSION: This study provides evidence for the usefulness of HRD analysis in all cancer types, improves chemotherapy decision making and its efficacy in clinical settings, and represents a substantial advancement in precision oncology | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Poly(ADP-ribose) Polymerase Inhibitors |2 NLM | |
| 700 | 1 | |a Brown, J B |e verfasserin |4 aut | |
| 700 | 1 | |a Yamaguchi, Ken |e verfasserin |4 aut | |
| 700 | 1 | |a Hamanishi, Junzo |e verfasserin |4 aut | |
| 700 | 1 | |a Yamanoi, Koji |e verfasserin |4 aut | |
| 700 | 1 | |a Takaya, Hisamitsu |e verfasserin |4 aut | |
| 700 | 1 | |a Kaneyasu, Tomoko |e verfasserin |4 aut | |
| 700 | 1 | |a Mori, Seiichi |e verfasserin |4 aut | |
| 700 | 1 | |a Mandai, Masaki |e verfasserin |4 aut | |
| 700 | 1 | |a Matsumura, Noriomi |e verfasserin |4 aut | |
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