{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:32:12Z","timestamp":1792773132262,"version":"4.5.0"},"reference-count":14,"publisher":"BMJ","issue":"9","funder":[{"DOI":"10.13039\/100010733","name":"B\u00f8rnecancerfonden","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100010733","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2026,5,28]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"\n We present two illustrative cases highlighting diagnostic, surveillance and management complexities of\n TP53<\/jats:italic>\n pathogenic variants (PVs). Case 1 describes a 24\u2010year\u2010old female with early-onset breast cancer and a somatic mosaic\n TP53<\/jats:italic>\n PV with a variant allele frequency of 19% in blood, initially missed by panel sequencing. Case 2 concerns a 59\u2010year\u2010old female with multiple primary tumours and two identical\n TP53<\/jats:italic>\n variants detected in two different tissues which initially suggested somatic mosaicism but were consistent with a myelodysplastic syndrome-related clone secondary to homozygous germline\n ERCC6L2<\/jats:italic>\n -associated bone marrow failure. These cases highlight the importance of accurately interpreting\n TP53<\/jats:italic>\n variants for correct clinical decision-making. Contextual factors such as age, phenotype, family history and tissue testing must guide diagnosis, treatment and surveillance.\n <\/jats:p>","DOI":"10.1136\/jmg-2025-111449","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T17:20:28Z","timestamp":1781025628000},"page":"569-572","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Interpreting\n TP53<\/i>\n variants: somatic mosaicism and\n ERCC6L2<\/i>\n -driven clonal evolution"],"prefix":"10.1136","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5446-4340","authenticated-orcid":false,"given":"Amalie Noergaard","family":"Andersson","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-5995","authenticated-orcid":false,"given":"Anna","family":"Byrjalsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida Elisabeth Viller","family":"Tuxen","sequence":"additional","affiliation":[{"name":"Department of Oncology, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette Klarskov","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4635-2653","authenticated-orcid":false,"given":"Thomas van Overeem","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Medicine, Copenhagen University, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2882-6798","authenticated-orcid":false,"given":"Karin A W","family":"Wadt","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Medicine, Copenhagen University, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"2026102307200982000_63.9.569.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-020-0638-4"},{"key":"2026102307200982000_63.9.569.2","first-page":"5358","article-title":"A cancer family syndrome in twenty-four kindreds","volume":"48","author":"Li","year":"1988","journal-title":"Cancer 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Predisposition to Myeloid Neoplasms in Adults: Recommendations for Genetic Diagnosis, Clinical Management and Follow-up","volume":"3","author":"Baliakas","year":"2019","journal-title":"Hemasphere"},{"key":"2026102307200982000_63.9.569.7","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022019425"},{"key":"2026102307200982000_63.9.569.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-023-05128-2"},{"key":"2026102307200982000_63.9.569.9","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017739"},{"key":"2026102307200982000_63.9.569.10","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1182\/blood.2025030230","article-title":"Bone marrow failure, somatic rescue by p53 inactivation, and enhanced leukemogenesis in germ line ERCC6L2 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