{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:32:20Z","timestamp":1793205140616,"version":"4.5.0"},"reference-count":47,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Macau Science and Technology Development Fund","award":["085\/2017\/A2"],"award-info":[{"award-number":["085\/2017\/A2"]}]},{"name":"Macau Science and Technology Development Fund","award":["0077\/2019\/AMJ"],"award-info":[{"award-number":["0077\/2019\/AMJ"]}]},{"name":"Macau Science and Technology Development Fund","award":["0032\/2022\/A1"],"award-info":[{"award-number":["0032\/2022\/A1"]}]},{"name":"Macau Science and Technology Development Fund","award":["SRG2017-00097-FHS"],"award-info":[{"award-number":["SRG2017-00097-FHS"]}]},{"name":"Macau Science and Technology Development Fund","award":["MYRG2019-00018-FHS"],"award-info":[{"award-number":["MYRG2019-00018-FHS"]}]},{"name":"Macau Science and Technology Development Fund","award":["MYRG2020-00094-FHS"],"award-info":[{"award-number":["MYRG2020-00094-FHS"]}]},{"name":"Macau Science and Technology Development Fund","award":["FHSIG\/SW\/0007\/2020P"],"award-info":[{"award-number":["FHSIG\/SW\/0007\/2020P"]}]},{"name":"University of Macau","award":["085\/2017\/A2"],"award-info":[{"award-number":["085\/2017\/A2"]}]},{"name":"University of Macau","award":["0077\/2019\/AMJ"],"award-info":[{"award-number":["0077\/2019\/AMJ"]}]},{"name":"University of Macau","award":["0032\/2022\/A1"],"award-info":[{"award-number":["0032\/2022\/A1"]}]},{"name":"University of Macau","award":["SRG2017-00097-FHS"],"award-info":[{"award-number":["SRG2017-00097-FHS"]}]},{"name":"University of Macau","award":["MYRG2019-00018-FHS"],"award-info":[{"award-number":["MYRG2019-00018-FHS"]}]},{"name":"University of Macau","award":["MYRG2020-00094-FHS"],"award-info":[{"award-number":["MYRG2020-00094-FHS"]}]},{"name":"University of Macau","award":["FHSIG\/SW\/0007\/2020P"],"award-info":[{"award-number":["FHSIG\/SW\/0007\/2020P"]}]},{"name":"Faculty of Health Sciences, University of Macau","award":["085\/2017\/A2"],"award-info":[{"award-number":["085\/2017\/A2"]}]},{"name":"Faculty of Health Sciences, University of Macau","award":["0077\/2019\/AMJ"],"award-info":[{"award-number":["0077\/2019\/AMJ"]}]},{"name":"Faculty of Health Sciences, University of Macau","award":["0032\/2022\/A1"],"award-info":[{"award-number":["0032\/2022\/A1"]}]},{"name":"Faculty of Health Sciences, University of Macau","award":["SRG2017-00097-FHS"],"award-info":[{"award-number":["SRG2017-00097-FHS"]}]},{"name":"Faculty of Health Sciences, University of Macau","award":["MYRG2019-00018-FHS"],"award-info":[{"award-number":["MYRG2019-00018-FHS"]}]},{"name":"Faculty of Health Sciences, University of Macau","award":["MYRG2020-00094-FHS"],"award-info":[{"award-number":["MYRG2020-00094-FHS"]}]},{"name":"Faculty of Health Sciences, University of Macau","award":["FHSIG\/SW\/0007\/2020P"],"award-info":[{"award-number":["FHSIG\/SW\/0007\/2020P"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>BRCAness refers to the damaged homologous recombination (HR) function due to the defects in HR-involved non-BRCA1\/2 genes. BRCAness is the important marker for the use of synthetic lethal-based PARP inhibitor therapy in breast and ovarian cancer treatment. The success provides an opportunity of applying PARP inhibitor therapy to treat other cancer types with BRCAness features. However, systematic knowledge is lack for BRCAness in different cancer types beyond breast and ovarian cancer. We performed a comprehensive characterization for 40 BRCAness-related genes in 33 cancer types with over 10,000 cancer cases, including pathogenic variation, homozygotic deletion, promoter hypermethylation, gene expression, and clinical correlation of BRCAness in each cancer type. Using BRCA1\/BRCA2 mutated breast and ovarian cancer as the control, we observed that BRCAness is widely present in multiple cancer types. Based on the sum of the BRCAneass features in each cancer type, we identified the following 21 cancer types as the potential targets for PARPi therapy: adrenocortical carcinoma, bladder urothelial carcinoma, brain lower grade glioma, colon adenocarcinoma, esophageal carcinoma, head and neck squamous carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, mesothelioma, rectum adenocarcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, sarcoma, skin cutaneous melanoma, stomach adenocarcinoma, uterine carcinosarcoma, and uterine corpus endometrial carcinoma.<\/jats:p>","DOI":"10.3390\/cells11233877","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T05:30:46Z","timestamp":1669872646000},"page":"3877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The BRCAness Landscape of Cancer"],"prefix":"10.3390","volume":"11","author":[{"given":"Maoni","family":"Guo","sequence":"first","affiliation":[{"name":"MoE Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-1320","authenticated-orcid":false,"given":"San Ming","family":"Wang","sequence":"additional","affiliation":[{"name":"MoE Frontiers Science Center for Precision Oncology, Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau 999078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1093\/carcin\/bgq069","article-title":"BRCA1 and BRCA2: Breast\/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair","volume":"31","author":"Livingston","year":"2010","journal-title":"Carcinogenesis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/cr.2008.1","article-title":"Homologous recombination in DNA repair and DNA damage tolerance","volume":"18","author":"Li","year":"2008","journal-title":"Cell Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nature10760","article-title":"The DNA damage response and cancer therapy","volume":"481","author":"Lord","year":"2012","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4704","DOI":"10.1093\/emboj\/20.17.4704","article-title":"Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences","volume":"20","author":"Tutt","year":"2001","journal-title":"EMBO J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8644","DOI":"10.1073\/pnas.151253498","article-title":"Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining","volume":"98","author":"Xia","year":"2001","journal-title":"Proc. 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