A Novel Germline TP53 Mutation in a Patient With Li-Fraumeni Syndrome: Resolving a Variant of Uncertain Significance. Issue 8 (November 2021)

• Record Type: Journal Article
• Authors: Douglass, David P.; Stine, Kimo C.; Farrar, Jason E.
• Is Part Of: Journal of pediatric hematology/oncology. Volume 43:Issue 8(2021)
• Publication Date: 2021-11
• Subjects: Li-Fraumeni syndrome -- IARC -- TP53 -- variant of uncertain significance; Pediatric hematology -- Periodicals; Tumors in children -- Periodicals; 618.9215
• DOI: 10.1097/MPH.0000000000002115
• Languages: English
• ISSNs: 1077-4114

Abstract

Abstract : Increasing availability of genomic testing poses new challenges to clinicians, particularly where variant interpretation from commercial sources may be equivocal. The authors report a patient with recurrent rhabdomyosarcoma and subsequent bilateral breast cancer who was found to harbor a previously undescribed germline TP53 sequence alteration annotated by the commercial laboratory as a variant of uncertain significance. By investigating publicly available databases of aggregated normal germline and malignant somatic genomic sequences, the authors conclude that this missense variant, c.476C>T (p.A159V), is a novel, pathogenic Li-Fraumeni syndrome mutation and demonstrate the utility of these resources in clinical pediatric hematology and oncology practice.