title: Early occurrence of lung adenocarcinoma and breast cancer after radiotherapy of a chest wall sarcoma in a patient with a de novo germline mutation in TP53.
abstract: We report a 26-year-old female patient who was diagnosed within 4 years with chest sarcoma, lung adenocarcinoma, and breast cancer. While her family history was unremarkable, DNA sequencing of TP53 revealed a germline de novo non-sense mutation in exon 6 p.Arg213X. One year later, she further developed a contralateral ductal carcinoma in situ, and 18 months later a jaw osteosarcoma. This case illustrates the therapeutic pitfalls in the care of a young cancer patient with TP53 de novo germline mutations and the complications related to her first-line therapy. Suggestion is made to use the less stringent Chompret criteria for germline TP53 mutation screening. Our observation underlines the possibly negative effect of radiotherapy in generating second tumors in patients with a TP53 mutation. We also present a review of six previously reported cases, comparing their cancer phenotypes with those generally produced by TP53 mutations.
authors.affiliation: Service de Génétique Médicale, CHUV, Lausanne, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrarini
authors.forename: Agnes
authors.initials: A
authors.lastname: Auteri-Kaczmarek
authors.forename: Alessia
authors.initials: A
authors.lastname: Pica
authors.forename: Nemya
authors.initials: N
authors.lastname: Boesch
authors.forename: Karl
authors.initials: K
authors.lastname: Heinimann
authors.forename: Stephan C
authors.initials: SC
authors.lastname: Schäfer
authors.forename: Sara
authors.initials: S
authors.lastname: Vesnaver-Megalo
authors.forename: Viviane
authors.initials: V
authors.lastname: Cina
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: Christian
authors.initials: C
authors.lastname: Monnerat
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology; D000328:Adult; D001943:Breast Neoplasms / Q000209:etiology; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology; D016609:Neoplasms, Second Primary / Q000209:etiology*; D012509:Sarcoma / Q000532:radiotherapy*; D013899:Thoracic Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D035441:Thoracic Wall; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53