{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T15:36:12Z","timestamp":1780414572594,"version":"3.54.1"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,12,30]],"date-time":"2023-12-30T00:00:00Z","timestamp":1703894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Institutional Science Foundation of Xi\u2019an Jiaotong University Medical College First Affiliated Hospital","award":["2019QN-07"],"award-info":[{"award-number":["2019QN-07"]}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2020JM-376"],"award-info":[{"award-number":["2020JM-376"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The presence of mutations in the BRCA1 gene (MIM: 113705) is widely recognized as a significant genetic predisposition for ovarian cancer. This study investigated the genomic mutations in a Chinese family with a history of ovarian, breast, and rectal adenocarcinoma. A novel germline mutation (Phe1695Val) in BRCA1 was identified through whole-exome sequencing. Subsequently, we performed whole-genome sequencing to identify somatic mutations and analyze mutational signatures in individuals carrying the novel germline mutation. Our findings revealed a correlation between somatic mutational signatures and the BRCA1 germline mutation in the proband with ovarian cancer, while no such association was observed in the tumor tissue from the patient with breast cancer. Furthermore, distinct somatic driver mutations were identified, a truncated mutation in the TP53 gene in the ovarian tumor tissue, and a hotspot mutation in the PIK3CA gene in the breast cancer. According to our findings, the BRCA1 F1695V mutation is linked to ovarian cancer susceptibility in the family and causes specific somatic mutational profiles.<\/jats:p>","DOI":"10.1093\/oncolo\/oyad294","type":"journal-article","created":{"date-parts":[[2023,12,30]],"date-time":"2023-12-30T14:57:23Z","timestamp":1703948243000},"page":"e837-e842","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Germline Mutation of <i>BRCA1<\/i> and Integrated Analysis With Somatic Mutation in a Chinese Multi-Cancer Family"],"prefix":"10.1093","volume":"29","author":[{"given":"Xiling","family":"Yang","sequence":"first","affiliation":[{"name":"Center for Translational Medicine, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"},{"name":"Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shang","sequence":"additional","affiliation":[{"name":"Maternal & Child Health Center, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"},{"name":"Shenzhen Health Development Research and Data Management Center , Shenzhen, Guangdong , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liren","family":"Yang","sequence":"additional","affiliation":[{"name":"Maternal & Child Health Center, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"},{"name":"School of Public Health, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Landi","family":"Sun","sequence":"additional","affiliation":[{"name":"Maternal & Child Health Center, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"},{"name":"School of Public Health, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Tuo","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"},{"name":"Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Ma","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"},{"name":"Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"},{"name":"Department of Obstetrics and Gynecology, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"},{"name":"Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"},{"name":"Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"},{"name":"Department of Obstetrics and Gynecology, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7799-5008","authenticated-orcid":false,"given":"Wenfang","family":"Yang","sequence":"additional","affiliation":[{"name":"Maternal & Child Health Center, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"},{"name":"Department of Obstetrics and Gynecology, Xi\u2019an Jiaotong University Medical College First Affiliated Hospital , Xi\u2019an, Shaanxi , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,30]]},"reference":[{"key":"2024060305564629300_CIT0001","first-page":"217","article-title":"Accurate classification of BRCA1 variants with saturation genome editing","volume-title":"Nature","author":"Findlay","year":"2018"},{"key":"2024060305564629300_CIT0002","first-page":"405","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume-title":"Genet Med","author":"Richards","year":"2015"},{"key":"2024060305564629300_CIT0003","first-page":"696","article-title":"The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers","volume-title":"Nat Rev Cancer","author":"Sondka","year":"2018"},{"key":"2024060305564629300_CIT0004","first-page":"362","article-title":"A mutation analysis of the BRCA1 gene in 140 families from southeast France with a history of breast and\/or ovarian cancer","volume-title":"J Hum Genet","author":"Rostagno","year":"2003"},{"key":"2024060305564629300_CIT0005","first-page":"572","article-title":"Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses","volume-title":"Nat Genet","author":"Zhang","year":"2020"},{"key":"2024060305564629300_CIT0006","first-page":"157","article-title":"Two genetic hits (more or less) to cancer","volume-title":"Nat Rev Cancer","author":"Knudson","year":"2001"},{"key":"2024060305564629300_CIT0007","first-page":"10086","article-title":"Patterns and functional implications of rare germline variants across 12 cancer types","volume-title":"Nat Commun","author":"Lu","year":"2015"},{"key":"2024060305564629300_CIT0008","first-page":"994","article-title":"The life history of 21 breast cancers","volume-title":"Cell","author":"Nik-Zainal","year":"2012"},{"key":"2024060305564629300_CIT0009","first-page":"979","article-title":"Mutational processes molding the genomes of 21 breast cancers","volume-title":"Cell","author":"Nik-Zainal","year":"2012"},{"key":"2024060305564629300_CIT0010","first-page":"1103","article-title":"Spectrum of TP53 mutations in BRCA1\/2 associated high-grade serous ovarian cancer","volume-title":"Front Oncol","author":"Boyarskikh","year":"2020"},{"key":"2024060305564629300_CIT0011","first-page":"341723","article-title":"Hereditary ovarian cancer: not only BRCA 1 and 2 genes","volume-title":"Biomed Res Int","author":"Toss","year":"2015"},{"key":"2024060305564629300_CIT0012","first-page":"78","article-title":"Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and\/or PTEN loss\/PTEN mutation","volume-title":"Breast Cancer Res","author":"Xing","year":"2019"},{"key":"2024060305564629300_CIT0013","first-page":"3140","article-title":"Comparison of BRCA versus non-BRCA germline mutations and associated somatic mutation profiles in patients with unselected breast cancer","volume-title":"Aging (Milano)","author":"Chen","year":"2020"},{"key":"2024060305564629300_CIT0014","first-page":"29","article-title":"A whole-genome massively parallel sequencing analysis of BRCA1 mutant oestrogen receptor-negative and -positive breast cancers","volume-title":"J Pathol","author":"Natrajan","year":"2012"},{"key":"2024060305564629300_CIT0015","first-page":"513","article-title":"Whole genome sequencing analysis for cancer genomics and precision medicine","volume-title":"Cancer Sci","author":"Nakagawa","year":"2018"},{"key":"2024060305564629300_CIT0016","first-page":"47","article-title":"Landscape of somatic mutations in 560 breast cancer whole-genome sequences","volume-title":"Nature","author":"Nik-Zainal","year":"2016"},{"key":"2024060305564629300_CIT0017","first-page":"415","article-title":"Signatures of mutational processes in human cancer","volume-title":"Nature","author":"Alexandrov","year":"2013"},{"key":"2024060305564629300_CIT0018","first-page":"489","article-title":"Whole-genome characterization of chemoresistant ovarian cancer","volume-title":"Nature","author":"Patch","year":"2015"},{"key":"2024060305564629300_CIT0019","first-page":"495","article-title":"Whole genomes redefine the mutational landscape of pancreatic cancer","volume-title":"Nature","author":"Waddell","year":"2015"},{"key":"2024060305564629300_CIT0020","first-page":"8683","article-title":"A mutational signature in gastric cancer suggests therapeutic strategies","volume-title":"Nat Commun","author":"Alexandrov","year":"2015"},{"key":"2024060305564629300_CIT0021","first-page":"11383","article-title":"The topography of mutational processes in breast cancer genomes","volume-title":"Nat Commun","author":"Morganella","year":"2016"},{"key":"2024060305564629300_CIT0022","first-page":"462","article-title":"The somatic genomic landscape of glioblastoma","volume-title":"Cell","author":"Brennan","year":"2013"},{"key":"2024060305564629300_CIT0023","first-page":"102668","article-title":"How do mutations affecting the breast cancer genes BRCA1 and BRCA2 cause cancer susceptibility","volume-title":"DNA Repair (Amst)","author":"Venkitaraman","year":"2019"},{"key":"2024060305564629300_CIT0024","first-page":"917","article-title":"Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy","volume-title":"Nature","author":"Farmer","year":"2005"},{"key":"2024060305564629300_CIT0025","first-page":"17041","article-title":"Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance","volume-title":"Proc Natl Acad Sci U S A","author":"Johnson","year":"2013"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyad294\/58038442\/oyad294.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyad294\/58038442\/oyad294.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T14:42:33Z","timestamp":1717425753000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/29\/6\/e837\/7504703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,30]]},"references-count":25,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,12,30]]},"published-print":{"date-parts":[[2024,6,3]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyad294","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,6,1]]},"published":{"date-parts":[[2023,12,30]]}}}