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Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients
Christine A Parkinson1,2,3,4,5, Davina Gale1,5, Anna M Piskorz1,5
1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
Plos Medicine
|December 21, 2016
Summary
Circulating tumor DNA (ctDNA) with TP53 mutations can monitor high-grade serous ovarian carcinoma (HGSOC) burden. A decrease in ctDNA after chemotherapy predicts treatment response and time to progression.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- Circulating tumor DNA (ctDNA) offers a minimally invasive method for assessing cancer burden and treatment response.
- Somatic TP53 mutations are a hallmark of high-grade serous ovarian carcinoma (HGSOC).
- This study investigates TP53 mutations as personalized markers for monitoring HGSOC.
Purpose of the Study:
- To evaluate TP53 mutations in ctDNA as a marker for monitoring tumor burden in HGSOC.
- To assess the utility of ctDNA in predicting treatment response and time to progression (TTP).
- To compare ctDNA dynamics with CA-125 and volumetric disease assessment.
Main Methods:
- Retrospective analysis of plasma samples from 40 HGSOC patients.
- Development of patient-specific TP53 mutation assays for ctDNA quantification using digital PCR.
- Comparison of TP53 mutant allele fraction (TP53MAF) with CA-125 and CT scan volumetric analysis.
Main Results:
- TP53MAF correlated with disease volume (r=0.59), with stronger correlation excluding ascites (r=0.82).
- Pre-treatment TP53MAF, unlike CA-125, was associated with TTP in relapsed disease.
- A decrease in TP53MAF >60% after one chemotherapy cycle independently predicted longer TTP (HR 0.22).
Conclusions:
- ctDNA, specifically TP53 mutations, correlates with HGSOC tumor volume.
- A significant decrease in TP53MAF post-chemotherapy is a sensitive early indicator of treatment response.
- ctDNA shows potential as a highly specific early molecular response marker in HGSOC, warranting further research.
