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Somatic TP53Mutations Are Detectable in Circulating Tumor DNA from Children with Anaplastic Wilms Tumors
- Source :
- Translational Oncology; December 2018, Vol. 11 Issue: 6 p1301-1306, 6p
- Publication Year :
- 2018
-
Abstract
- BACKGROUND:Diffuse anaplastic Wilms tumor (DAWT) is a rare, high-risk subtype that is often missed on diagnostic needle biopsy. Somatic mutations in TP53are associated with the development of anaplasia and with poorer survival, particularly in advanced-stage disease. Early identification of DAWT harboring TP53abnormalities could improve risk stratification of initial therapy and monitoring for recurrence. METHODS:Droplet digital polymerase chain reaction (ddPCR) was used to evaluate 21 samples from 4 patients with DAWT. For each patient, we assessed TP53status in frozen tumor, matched germline DNA, and circulating tumor DNA (ctDNA) from plasma, serum, and urine collected throughout treatment. RESULTS: Mutant TP53was detectable in ctDNA from plasma and serum in all patients. We did not detect variant TP53in the same volume (200 μl) of urine. One patient displayed heterogeneity of TP53in the tumor despite both histological sections displaying anaplasia. Concentration of ctDNA from plasma/serum taken prenephrectomy varied significantly between patients, ranging from 0.44 (0.05-0.90) to 125.25 (109.75-140.25) copies/μl. We observed variation in ctDNA throughout treatment, and in all but one patient, ctDNA levels fell significantly following nephrectomy. CONCLUSION:We demonstrate for the first time that ddPCR is an effective method for detection of mutant TP53in ctDNA from children with DAWT even when there is intratumoral somatic heterogeneity. This should be further explored in a larger cohort of patients, as early detection of circulating variant TP53may have significant clinical impact on future risk stratification and surveillance.
Details
- Language :
- English
- ISSN :
- 19447124 and 19365233
- Volume :
- 11
- Issue :
- 6
- Database :
- Supplemental Index
- Journal :
- Translational Oncology
- Publication Type :
- Periodical
- Accession number :
- ejs46390484
- Full Text :
- https://doi.org/10.1016/j.tranon.2018.08.006