{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:44:12Z","timestamp":1771922652448,"version":"3.50.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pathogenic\n                      <jats:italic>BRCA1<\/jats:italic>\n                      variants are established in hereditary breast and ovarian cancer (HBOC) and associated with pancreatic, prostate, and gastric cancers. Salivary gland tumors (SGTs) have been reported in\n                      <jats:italic>BRCA1\/2<\/jats:italic>\n                      carriers and suggested as part of an extended HBOC phenotype based on epidemiological associations. However, functional evidence is lacking, and homologous recombination deficiency (HRD)\u2014the hallmark of BRCA-driven cancers\u2014has not been systematically assessed in\n                      <jats:italic>BRCA1<\/jats:italic>\n                      -associated SGTs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We report a Colombian family segregating the\n                      <jats:italic>BRCA1<\/jats:italic>\n                      c.3331_3334delCAAG (p.Gln1111Asnfs*5) founder variant with phenotypic variability across four generations: gastric (31%), breast (37.5%), colorectal (19%), and thyroid cancers (12.5%). The proband, a 61-year-old woman, developed high-grade mucoepidermoid carcinoma of the parotid gland. Germline testing confirmed the familial BRCA1 variant. Tumor profiling revealed the same BRCA1 variant (VAF 56%) plus a pathogenic TP53 mutation (c.730G&amp;gt;T, p.Gly244Cys; VAF 32%), without\n                      <jats:italic>BRCA1<\/jats:italic>\n                      loss of heterozygosity. HRD testing using shallow whole genome sequencing showed preserved homologous recombination function (Genomic Instability Score: 0.01, LGA: 11.40, LPC: 0), all below HRD-positive thresholds.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This represents the first SGT in a\n                      <jats:italic>BRCA1<\/jats:italic>\n                      carrier evaluated with HRD testing. The absence of HRD argues against BRCA1-driven tumorigenesis despite clear familial segregation. These findings challenge the presumed causal relationship between BRCA1 variants and SGT development. Clinical implications are direct: SGTs in\n                      <jats:italic>BRCA1<\/jats:italic>\n                      carriers should not be assumed eligible for PARP inhibitor therapy without HRD confirmation, and enhanced surveillance appears unwarranted. This case underscores that co-occurrence does not establish causation and highlights the critical importance of functional validation before expanding hereditary cancer spectra.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2025.1692001","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:35:32Z","timestamp":1768973732000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Challenging the extended phenotype: HRD-negative salivary gland carcinoma in a BRCA1 founder-variant carrier, case report and literature review"],"prefix":"10.3389","volume":"15","author":[{"given":"William","family":"Torres","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Oncology, Instituto Nacional de Cancerolog\u00eda","place":["Bogot\u00e1, D.C, Colombia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Vargas","sequence":"additional","affiliation":[{"name":"Career Researcher, Hospital Universitario Mayor-M\u00e9deri, Universidad del Rosario","place":["Bogot\u00e1, D.C, Colombia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego-Felipe","family":"Ballen","sequence":"additional","affiliation":[{"name":"Clinical Oncology Unit, Instituto Nacional de Cancerolog\u00eda","place":["Bogot\u00e1, D.C, Colombia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra M","family":"Tapiero-Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Oncology, Instituto Nacional de Cancerolog\u00eda","place":["Bogot\u00e1, D.C, Colombia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique","family":"Cadena","sequence":"additional","affiliation":[{"name":"Head and Neck Surgery Unit, Instituto Nacional de Cancerolog\u00eda","place":["Bogot\u00e1, D. 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