{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:11:34Z","timestamp":1792696294570,"version":"4.5.0"},"reference-count":31,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precision Oncology"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Multigene panel testing (MGPT) identifies TP53 pathogenic or likely pathogenic (P\/LP) variants in patients with diverse phenotypes, of which only one is classic Li-Fraumeni syndrome. Low variant allelic fraction (VAF) in TP53 found on germline testing may suggest aberrant clonal expansion or constitutional mosaicism. We evaluated TP53-positive probands seen in a cancer genetics program to determine germline versus somatic status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We reviewed TP53-positive probands from 2012 to 2019 identified by MGPT on blood or saliva (N = 84). Available VAFs were collected. Probands with a familial variant, who met Li-Fraumeni syndrome testing criteria or who carried a founder variant, were considered germline. For those with uncertain germline status, TP53 variants were further examined using ancillary data of family members and somatic tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Of the 84 probands, 54.7% had germline variants with 33.3% meeting criteria for germline status and 21.4% confirmed through ancillary testing. Aberrant clonal expansion comprised 13.1% with clonal hematopoiesis of indeterminate potential and 2.4% with a hematologic malignancy. Constitutional mosaicism was confirmed in 8.3% probands. Definitive status could not be determined in 3.6% despite ancillary assessment, and 17.9% did not have ancillary testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>A TP53 P\/LP variant found on peripheral blood or saliva MGPT does not always originate in the germline. In a clinical cancer genetics cohort, approximately half of the patients had TP53 P\/LP germline variants; these patients plus those with constitutional mosaicism require intensified surveillance. A framework of multiple strategies enables discernment of germline from constitutional mosaic and acquired variants, which is essential for appropriate management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po.21.00278","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T15:59:00Z","timestamp":1635955140000},"page":"1677-1686","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":18,"title":["Evaluation of\n                    <i>TP53<\/i>\n                    Variants Detected on Peripheral Blood or Saliva Testing: Discerning Germline From Somatic\n                    <i>TP53<\/i>\n                    Variants"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3861-4203","authenticated-orcid":false,"given":"Alison N.","family":"Schwartz","sequence":"first","affiliation":[{"name":"Division of Cancer Genetics and Prevention, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-0113","authenticated-orcid":false,"given":"Sophie R.","family":"Cahill","sequence":"additional","affiliation":[{"name":"Division of Cancer Genetics and Prevention, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha M.","family":"Stokes","sequence":"additional","affiliation":[{"name":"Division of Cancer Genetics and Prevention, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Castillo","sequence":"additional","affiliation":[{"name":"Division of Clinical Cancer Genomics, Beckman Research Institute, City of Hope, Duarte, 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