Monitoring dynamic cytotoxic chemotherapy response in castration-resistant prostate cancer using plasma cell-free DNA (cfDNA)

BMC Research Notes

Katherin Patsch¹  David B. Agus¹  Naim Matasci¹  Patricia Diaz¹  Daniel Ruderman¹  Mitchell E. Gross¹  Anjana Soundararajan¹ 

[1] 0000 0001 2156 6853, grid.42505.36, Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA, USA;

关键词: Cell-free DNA;    Chemotherapy;    Prostate cancer;    Androgen receptor;    Sequencing;   

DOI  :  10.1186/s13104-019-4312-2

来源: publisher

【 摘 要 】

ObjectiveCell-free DNA (cfDNA) is an attractive cancer biomarker, as it is thought to reflect a component of the underlying genetic makeup of the tumor and is readily accessible in serial fashion. Because chemotherapy regimens are expected to act rapidly on cancer and cfDNA is cleared from the blood within minutes, we hypothesized that cfDNA would reflect immediate effects of treatment. Here, we developed a method for monitoring long cfDNA fragments, and report dynamic changes in response to cytotoxic chemotherapy.ResultsPeripheral blood was obtained from 15 patients with metastatic castration-resistant prostate cancer (CRPC) immediately before and after cytotoxic chemotherapy infusion. cfDNA was extracted and quantified for long interspersed nuclear elements (LINE1; 297 bp) using qPCR. Targeted deep sequencing was performed to quantify the frequency of mutations in exon 8 of the androgen receptor (AR), a mutational hotspot region in CRPC. Single nucleotide mutations in AR exon 8 were found in 6 subjects (6/15 = 40%). Analytical variability was minimized by pooling independent PCR reactions for each library. In 5 patients, tumor-derived long cfDNA levels were found to change immediately after infusion. Detailed analysis of one subject suggests that cytotoxic chemotherapy can produce rapidly observable effects on cfDNA.

【 授权许可】

CC BY