{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:38:06Z","timestamp":1788233886485,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,9,30]],"date-time":"2017-09-30T00:00:00Z","timestamp":1506729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Hellenic Cooperative Oncology Group internal research grant","award":["HE\u00a0R_5G"],"award-info":[{"award-number":["HE\u00a0R_5G"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>Genomic patterns of nasopharyngeal carcinomas (NPCs) have as yet been studied in Southeast Asian (SEA) patients. Here, we investigated genomic patterns of locally advanced NPC Southeast European (SEE) patients treated with chemoradiotherapy. We examined 126 tumors (89% EBV positive) from Greek and Romanian NPC patients with massively parallel sequencing. Paired tumor\u2010cell\u2010rich (TC) and infiltrating\u2010lymphocyte\u2010rich (TILs) samples were available in 19 and paired tumor\u2010germline samples in 68 cases. Top mutated genes were <jats:italic>BRCA1<\/jats:italic> (54% of all tumors); <jats:italic>BRCA2<\/jats:italic> (29%); <jats:italic>TP53<\/jats:italic> (22%); <jats:italic>KRAS<\/jats:italic> (18%). Based on the presence and number of mutations and mutated genes, NPC were classified as stable (no mutations, <jats:italic>n<\/jats:italic>\u2009=\u200927); unstable (&gt;7 genes with multiple mutations, all <jats:italic>BRCA1<\/jats:italic> positive, <jats:italic>n<\/jats:italic>\u2009=\u200921); and of intermediate stability (1\u20137 singly mutated genes, <jats:italic>n<\/jats:italic>\u2009=\u200978). <jats:italic>BRCA1<\/jats:italic> p.Q563* was present in 59 tumors (48%), more frequently from Romanian patients (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). No pathogenic germline mutations were identified. NPC exhibited <jats:italic>APOBEC3A\/B<\/jats:italic> and nucleotide\u2010excision\u2010repair\u2010related mutational signatures. As compared to TC, TILs demonstrated few shared and a higher number of low frequency private mutations (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). In multivariate analysis models for progression\u2010free survival, EBV positivity was a favorable prognosticator in stable tumors; <jats:italic>BRCA1<\/jats:italic> mutations were unfavorable only in tumors of intermediate stability. In conclusion, other than described for SEA NPC, somatic <jats:italic>BRCA1<\/jats:italic> mutations were common in SEE NPC; these were shared between TC and TILs, and appeared to affect patient outcome according to tumor genomic stability status. Along with the identified mutational signatures, these novel data may be helpful for designing new treatments for locally advanced NPC.<\/jats:p>","DOI":"10.1002\/ijc.31023","type":"journal-article","created":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T12:05:57Z","timestamp":1504181157000},"page":"66-80","source":"Crossref","is-referenced-by-count":21,"title":["Prevalent somatic <i>BRCA1<\/i> mutations shape clinically relevant genomic patterns of nasopharyngeal carcinoma in Southeast Europe"],"prefix":"10.1002","volume":"142","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8045-2186","authenticated-orcid":false,"given":"George","family":"Fountzilas","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Oncology Hellenic Foundation for Cancer Research\/Aristotle University of Thessaloniki Thessaloniki Greece"},{"name":"Faculty of Medicine, School of Health Sciences Aristotle University of Thessaloniki Thessaloniki 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Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelos","family":"Koutras","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Medicine University Hospital, University of Patras Medical School Patras Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Psoma","sequence":"additional","affiliation":[{"name":"Department of Radiology AHEPA Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kalogera\u2010Fountzila","sequence":"additional","affiliation":[{"name":"Department of Radiology AHEPA Hospital, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Skondra","sequence":"additional","affiliation":[{"name":"Oncology Section, 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