{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T20:09:26Z","timestamp":1779480566388,"version":"3.53.1"},"reference-count":20,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Germline likely pathogenic or pathogenic variants (LP\/PV) in the\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      proto-oncogene account for approximately 25% of medullary thyroid cancers (MTCs). Depending on the variant, individuals with\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      LP\/PV can have &gt; 70% lifetime risk for MTC or C-cell hyperplasia, an MTC precursor. We assessed prevalence and genotype-phenotype correlations of\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      LP\/PV in a pan-cancer population undergoing agnostic multigene germline cancer genetic testing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Patients with cancer at Memorial Sloan Kettering Cancer Center provided informed consent to Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, a paired tumor-normal genomic sequencing protocol (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT01775072\">NCT01775072<\/jats:ext-link>\n                      ) from 2015 to 2023. Consent included multigene germline testing inclusive of\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      . LP\/PVs in\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      were categorized per standardized MTC risk levels. Clinical data, including family history, surveillance results, and pathology, were extracted from medical records.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Twenty-one of 31,866 patients harbored an LP\/PV in the\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      gene, with the most common variant being p.Val804Met (n = 10) of moderate risk. Although six patients had a personal history of MTC, 15 of 21 patients (71%) had neither a personal nor a family history of MTC. Of the 15, nine underwent endocrinology high-risk surveillance, with five patients deciding to proceed with thyroidectomy due to abnormal surveillance findings. Pathologic findings consisted of isolated C-cell hyperplasia only (n = 1), microMTC and C-cell hyperplasia (n = 2), stage I MTC and C-cell hyperplasia (n = 1), and stage IVA MTC (n = 1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      In this pan-cancer cohort, 71% of\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      LP\/PV findings were incidental, with no prior personal or family history of MTC. High-risk surveillance and potential thyroidectomy are warranted in patients with an incidental germline\n                      <jats:italic toggle=\"yes\">RET<\/jats:italic>\n                      LP\/PV finding due to high rates of precursor lesions and MTC even among these patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00737","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T19:59:16Z","timestamp":1779479956000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Prevalence of Germline Pathogenic\n                    <i>RET<\/i>\n                    Variants in a Pan-Cancer Patient Population"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3902-6054","authenticated-orcid":true,"given":"Matilde","family":"Borio","sequence":"first","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Sheehan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Katabi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalba E.","family":"Sacca","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Maio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5042-5651","authenticated-orcid":true,"given":"Yelena","family":"Kemel","sequence":"additional","affiliation":[{"name":"Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliya","family":"Khurram","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4154-0567","authenticated-orcid":true,"given":"Diana","family":"Mandelker","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozge","family":"Birsoy","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6614-802X","authenticated-orcid":true,"given":"David","family":"Solit","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Weill Cornell Medical College, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4786-7408","authenticated-orcid":true,"given":"Maria I.","family":"Carlo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Weill Cornell Medical College, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5790-851X","authenticated-orcid":true,"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Weill Cornell Medical College, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Abbass","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Weill Cornell Medical College, New York, NY"},{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7682-0350","authenticated-orcid":true,"given":"Lauren","family":"Banaszak","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chimene","family":"Kesserwan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9027-2891","authenticated-orcid":true,"given":"Yonina R.","family":"Murciano-Goroff","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Weill Cornell Medical College, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9758-713X","authenticated-orcid":true,"given":"Alicia","family":"Latham","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Weill Cornell Medical College, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2180-2032","authenticated-orcid":true,"given":"Kenneth","family":"Offit","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Weill Cornell Medical College, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Wong","sequence":"additional","affiliation":[{"name":"Weill Cornell Medical College, New York, NY"},{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2802-8489","authenticated-orcid":true,"given":"Ronald","family":"Ghossein","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, 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