Abstract 1198P
Background
TP53 mutations are present in almost all BRCA1-associated hereditary breast tumours and high-grade serous ovarian carcinomas (OC). Therefore, they are likely to be useful for disease monitoring by liquid biopsy.
Methods
Single or serial plasma samples were obtained from 10 patients with OC (8 BRCA1 mutation carriers, 1 CHEK2 mutation carrier and 1 sporadic OC) and 7 women with BRCA1-associated breast cancer. Somatic mutation status for TP53 and some other genes was determined in archival tumour material by the next generation sequencing. Individual digital droplet PCR-based tests were developed for 16 identified TP53 mutations as well as for BRAF V600E substitution detected in the CHEK2-associated OC.
Results
All but one plasma samples obtained from OC patients before the treatment or at the time of disease progression were positive for TP53 mutations (6 samples from 4 patients). In contrast, plasma samples taken either at the time of clinical remission (1-2 years after completion of the treatment; 5 samples from 4 patients) or immediately after optimal cytoreductive surgery (1 sample) were negative for circulating tumour-specific mutations. All plasma samples from stage II-III breast cancer patients, including 4 taken at the diagnosis, 2 obtained after completion of the treatment and 7 collected within the period of the disease remission, were negative for tumour-specific TP53 alterations.
Conclusions
There is a good correlation between the presence of tumour-specific TP53 mutation in circulating DNA and the disease status in OC patients, therefore TP53 is a promising marker for clinical monitoring of ovarian cancer. TP53 mutation cannot be reliably detected by digital droplet PCR in the plasma of breast cancer patients, who have moderate disease burden.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Russian Science Foundation.
Disclosure
All authors have declared no conflicts of interest.