{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:46:00Z","timestamp":1791924360527,"version":"4.3.4"},"reference-count":67,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Skin adnexal carcinomas (SACs) are rare and heterogeneous tumors with no established systemic treatment options and poor long-term survival rates in the advanced disease setting. Here, we aimed to characterize the genomic landscape and clinically actionable alterations across SAC subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed next-generation sequencing data from SACs in the American Association for Cancer Research Project GENIE. Mutations, copy number alterations, and structural variants were annotated using OncoKB. Actionable alterations were defined as Level 1-2 alterations or tumor mutational burden (TMB) \u226510 mut\/Mb. TMB was compared across subtypes and with melanoma, cutaneous squamous cell carcinoma (CSCC), and basal cell carcinoma (BCC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 224 SACs were analyzed (49% extramammary Paget disease [EMPD], 33% apocrine\/eccrine, 17% sebaceous, 1% follicular). In EMPD, the most frequent actionable alterations were in\n                      <jats:italic toggle=\"yes\">PIK3CA<\/jats:italic>\n                      (25.7%) and\n                      <jats:italic toggle=\"yes\">ERBB2<\/jats:italic>\n                      (22.9%). In sebaceous carcinoma, actionable alterations were mainly in\n                      <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n                      (10.3%) and\n                      <jats:italic toggle=\"yes\">PIK3CA<\/jats:italic>\n                      (10.3%). Apocrine\/eccrine tumors also presented\n                      <jats:italic toggle=\"yes\">ERBB2<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">PIK3CA<\/jats:italic>\n                      alterations, but at lower frequencies (5.5% and 8.2%, respectively). TMB-high occurred in 10.1% of EMPD, 28.2% of sebaceous, and 21.9% of apocrine\/eccrine tumors, lower than in melanoma (52.1%), CSCC (64.4%), and BCC (63.3%). SAC drivers showed important heterogeneity across subtypes. Overall, 48.2% of SACs harbored at least one potentially actionable alteration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SACs frequently harbor clinically actionable alterations in a histotype-dependent manner. The identification of lineage-specific genomic differences underscores the clinical and translational relevance of integrating histology with genomic profiling for guiding therapeutic decision making.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-26-00300","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:59:07Z","timestamp":1791921547000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Genomic Landscape and Clinical Actionability of Skin Adnexal Carcinomas"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2864-0966","authenticated-orcid":true,"given":"Valbert Oliveira","family":"Costa Filho","sequence":"first","affiliation":[{"name":"Faculdade de Medicina, Universidade Federal do Ceara, Fortaleza, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0889-7425","authenticated-orcid":true,"given":"Mariana Macambira","family":"Noronha","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade Federal do Ceara, Fortaleza, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9049-0996","authenticated-orcid":true,"given":"Pedro Robson","family":"Costa Passos","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade Federal do Ceara, Fortaleza, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4988-644X","authenticated-orcid":true,"given":"Carlos Diego","family":"Holanda Lopes","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology &amp; Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada"},{"name":"Department of Medicine, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1848-4480","authenticated-orcid":true,"given":"Giuseppe G.F.","family":"Leite","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Escola Paulista de Medicina Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9915-0106","authenticated-orcid":true,"given":"Danielle Calheiros Campelo","family":"Maia","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade Federal do Ceara, Fortaleza, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Wagner","family":"de Souza Wanderley","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel D.","family":"Saibil","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology &amp; Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada"},{"name":"Department of Medicine, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7972-4244","authenticated-orcid":true,"given":"Erick F.","family":"Saldanha","sequence":"additional","affiliation":[{"name":"Department of Cutaneous Oncology, H. 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