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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Interpreting TP53 variants: somatic mosaicism and ERCC6L2-driven clonal evolution
Amalie Noergaard Andersson1, Anna Byrjalsen1, Ida Elisabeth Viller Tuxen2
1Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.
Abstract:
We present two illustrative cases highlighting diagnostic, surveillance and management complexities of TP53 pathogenic variants (PVs). Case 1 describes a 24-year-old female with early-onset breast cancer and a somatic mosaic TP53 PV with a variant allele frequency of 19% in blood, initially missed by panel sequencing. Case 2 concerns a 59-year-old female with multiple primary tumours and two identical TP53 variants detected in two different tissues which initially suggested somatic mosaicism but were consistent with a myelodysplastic syndrome-related clone secondary to homozygous germline ERCC6L2-associated bone marrow failure. These cases highlight the importance of accurately interpreting TP53 variants for correct clinical decision-making. Contextual factors such as age, phenotype, family history and tissue testing must guide diagnosis, treatment and surveillance.
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