A PATHOGENIC TP53 GENE C.154C>T (P.GLN52TER) NONSENSE VARIANT IN A WOMAN WITH EARLY-ONSET BREAST CANCER: A CASE REPORT

Abstract

Relevance: Pathogenic constitutional variants of Tumor Protein 53 (TP53) underlie Li-Fraumeni syndrome and confer susceptibility to several malignancies that may arise at unusually young ages. Breast cancer diagnosed before 31 years is included in the modified Chompret criteria for TP53 testing, irrespective of family history. Evidence concerning rare TP53 alterations in Central Asian populations remains scarce.The study aimed to present the clinical and molecular characteristics of early-onset breast cancer in a patient with the TP53 gene variant NM_000546.6:c.154C>T (NP_000537.3:p.Gln52Ter).Materials and Methods: This report concerns a Kazakh woman whose breast cancer was diagnosed at 28 years of age. We retrieved clinical and pathological information from medical records. DNA isolated from peripheral blood was examined with the TruSight Cancer Sequencing Panel on an Illumina MiSeq instrument. Sanger sequencing independently verified the selected TP53 finding.Results: In 2008, the patient was diagnosed with stage IIIA (T3N1M0) nodular carcinoma of the right breast. Histological assessment showed grade 2 invasive ductal carcinoma. The tumor was negative for estrogen receptor, progesterone receptor, and Human Epidermal Growth Factor Receptor 2 (HER2) expression, with a Ki-67 index of 98%. Following approximately seven years of remission, progression was recorded in 2015, with supraclavicular lymph node involvement and a lesion in the contralateral breast. The patient died of progressive cancer in 2019. Sequencing revealed the heterozygous TP53 variant NM_000546.6:c.154C>T (NP_000537.3:p.Gln52Ter), which introduces a premature termination codon p.Gln52Ter.Conclusion: The combination of very early-onset breast cancer, aggressive clinical features, contralateral breast involvement, and the observed truncating TP53 c.154C>T (p.Gln52Ter) variant supports TP53-related cancer susceptibility despite a negative family history. The case emphasizes the importance of phenotype-based genetic evaluation in young patients and provides additional evidence from an underrepresented Central Asian population.