{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:10:52Z","timestamp":1789575052090,"version":"build-2803163510"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hereditary cancers arise from germline pathogenic variants that confer increased lifetime cancer risk. In Palestine, the genetic basis of hereditary cancer predisposition remains limited. The objective of this study is to investigate germline variants associated with hereditary cancer susceptibility in Palestinian families with strong cancer history.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Families with suspected hereditary breast cancer were recruited, and germline DNA extracted from peripheral blood was first analyzed using a BRCA1\/2 panel. Whole-exome sequencing (WES) was subsequently performed in BRCA-negative probands to identify additional candidate hereditary variants. A total of 34 individuals from three unrelated families were included in the study, comprising 8 affected and 26 unaffected individuals. Segregation analysis and in silico functional assessment were conducted to evaluate variant pathogenicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified a splice\u2010site variant in RAD50 (c.2524+3A&amp;gt;G) in Family I, a truncating MSH4 variant (c.328C&amp;gt;T; p.R110X) and a missense STAT6 variant (c.1216C&amp;gt;G; p.L406V) in Family II, and a splice\u2010region PRKAR1A variant (c.973+6T&amp;gt;C) in Family III. These variants are segregated with disease in the respective families and are predicted to affect protein function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings highlight the importance of germline genomic analysis in characterizing hereditary cancer predisposition in underrepresented populations and provide preliminary data for future risk assessment and genetic counseling strategies in Palestine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1779001","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T22:10:31Z","timestamp":1781734231000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Utilization of whole exome sequencing to identify hereditary mutations in Palestinian families with hereditary cancers"],"prefix":"10.3389","volume":"17","author":[{"given":"Nouar","family":"Qutob","sequence":"first","affiliation":[{"name":"Faculty of Graduate Studies, Arab American University","place":["Ramallah, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musa","family":"Hindiyeh","sequence":"additional","affiliation":[{"name":"Augusta Victoria Hospital","place":["J\u00e9rusalem, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fouad","family":"Zahdeh","sequence":"additional","affiliation":[{"name":"Faculty of Graduate Studies, Arab American University","place":["Ramallah, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akram","family":"Alian","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Utah School of Medicine","place":["Salt Lake City, UT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rua","family":"Thawabteh","sequence":"additional","affiliation":[{"name":"Faculty of Graduate Studies, Arab American University","place":["Ramallah, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Husam","family":"Sallam","sequence":"additional","affiliation":[{"name":"Faculty of Graduate Studies, Arab American University","place":["Ramallah, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdallah","family":"Natsheh","sequence":"additional","affiliation":[{"name":"Faculty of Graduate Studies, Arab American University","place":["Ramallah, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s13104-018-3310-0","article-title":"CHRNA5 and CHRNA3 polymorphism and lung cancer susceptibility in the Palestinian population","volume":"11","author":"Ayesh","year":"2018","journal-title":"BMC Res. 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