Tumor DNA has been detected in body fluids of cancer patients. Somatic tumor mutations are being used as biomarkers in body fluids to monitor chemotherapy response as a minimally invasive tool. In this study, we evaluated the potential of tracking somatic mutations in free DNA of plasma and urine collected from Wilms tumor (WT) patients for monitoring treatment response. Wilms tumor is a pediatric renal tumor resulting from cell differentiation errors during nephrogenesis. Its mutational repertoire is not completely defined. Thus, for identifying somatic mutations from tumor tissue DNA, we screened matched tumor/leukocyte DNAs using either a panel containing 16 WT‐associated genes or whole‐exome sequencing (WES). The identified somatic tumor mutations were tracked in urine and plasma DNA collected before, during and after treatment. At least one somatic mutation was identified in five out of six WT tissue samples analyzed. Somatic mutations were detected in body fluids before treatment in all five patients (three patients in urine, three in plasma, and one in both body fluids). In all patients, a decrease of the variant allele fraction of somatic mutations was observed in body fluids during neoadjuvant chemotherapy. Interestingly, the persistence of somatic mutations in body fluids was in accordance with clinical parameters. For one patient who progressed to death, it persisted in high levels in serial body fluid samples during treatment. For three patients without disease progression, somatic mutations were not consistently detected in samples throughout monitoring. For one patient with bilateral disease, a somatic mutation was detected at low levels with no support of clinical manifestation. Our results demonstrated the potential of tracking somatic mutations in urine and plasma DNA as a minimally invasive tool for monitoring WT patients. Additional investigation is needed to check the clinical value of insistent somatic mutations in body fluids.
Detection of tumor DNA in urine has been shown as viable method of diagnosis not only for urinary tract (e.g., kidney and bladder) cancers but also for other types, e.g. prostate. Applications of such method, resemble those which use plasma DNA and include cancer detection, monitoring of tumor growth or recurrence and response to chemotherapy or radiation therapy. As far as we know, there is a lack of studies applying urine DNA detection in Wilms tumor (WT), an embryonary kidney cancer type. Here we show evidences of detection for two somatic variants in the urine DNA of one WT patient. By using NGS exome sequencing of tumor tissue and leukocytes samples of the same patient we were able to find new somatic variants: a frame-shift indel in TNRC18 and a misssense SNV in INTS1 gene. Target sequencing applied to the DNA from the patient's urine revealed the presence of these two somatic variants. More interestingly, both variants could not be found in the urine DNA of this patient after treatment (chemotherapy and nephrectomy). Additionally, these genes are poorly characterized in WT contributing for the comprehension of the cellular processes that are operating in tumorigenesis of WT. Altogether, our findings contribute with the mutational repertoire of WT and reveals the potential of using urine DNA sequencing as a noninvasive cancer screening approach. Citation Format: Ana C. K. Miguez, Rodrigo F. Ramalho, Elisa N. Ferreira, Bruna D. F. Barros, Claudia A. A. de Paula, Renan Valieris, Louise D. C. Mota, Jorge E. Souza, Isabela W. Cunha, Cecília L. Costa, Sandro J. de Souza, Dirce M. Carraro. Urine as a potential liquid biopsy for detecting tumor DNA in Wilms tumor patient: Detection of somatic mutations in urine opens perspectives of monitoring chemotherapy response in WT patients. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr A32.
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