image: Kaplan–Meier DFS estimates. view more
Credit: Correspondence to - Flora Zagouri - florazagouri@yahoo.co.uk
Oncotarget published "TP53 mutations determined by targeted NGS in breast cancer: a case-control study" which reported that the purpose of our study is to evaluate the role of TP53 somatic mutations detected via next-generation sequencing as a potential prognostic marker in patients with breast cancer.
23 cases of somatic TP53 mutations and 23 cases of healthy controls were matched on age at diagnosis, menopausal status, histological subtype, histological grade, ki67 expression and disease stage. Co-existence of PIK3CA mutation was a common finding in somatic TP53-mutant tumors. Disease-free survival was shorter in TP53-mutated cases.
TP53 pathogenic somatic mutations were associated with a 8-fold risk of recurrence in the univariate Cox regression analysis. This case-control study suggests that TP53 somatic mutations detected by next-generation sequencing are associated with an adverse prognosis in breast cancer.
Dr. Flora Zagouri from The Alexandra Hospital Medical School said, "TP53 gene is the most frequently mutated gene (>50%) in human cancer, indicating its crucial role as a tumor suppressor."
TP53 gene encodes the p53 protein which is considered as «the guardian of the genome» by binding to specific DNA sequences and maintaining genomic stability. P53 protein is involved in cell response to stress signals, activates DNA repair proteins and regulates the production of stem cells. The fundamental role of TP53 is evident in Li-Fraumeni syndrome which is characterized by germline mutations of TP53 and predisposition to aggressive tumors like early-onset breast cancer, soft-tissue or bone sarcomas and brain tumors. More recently, next generation sequencing has allowed the detection of TP53 mutations outside this restricted region.
There are numerous studies assessing the clinical significance of TP53 mutations in breast cancer. However, the results of these studies are often contradicting. P53 mutation was associated with negative estrogen and progesterone receptor status and increased mortality rate in 859 breast cancer women. TP53 mutations within exons 5 to 8 detected by gene sequencing were related to increased risk of breast cancer-specific death regardless of tumor size, nodal status and hormone receptor expression. Moreover, P53 mutation status has been associated with response to breast cancer treatment.
The Zagouri Research Team concluded in their Oncotarget Research Output, "We here show that TP53 pathogenic somatic mutations are associated with a shorter DFS in early-stage breast cancer patients. In addition, TP53 mutations often coexist with PIK3CA mutations in breast tumors (17.4%). Future well designed studies should be performed to address the clinical role of the co-existence of these mutations in breast cancer."
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DOI - https://doi.org/10.18632/oncotarget.28071
Full text - https://www.oncotarget.com/article/28071/text/
Correspondence to - Flora Zagouri - florazagouri@yahoo.co.uk
Keywords - TP53 mutations, next-generation sequencing, biomarker, prognosis,breast cancer
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