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Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer

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Published on: November 2, 2013

Cell-Free DNA Genomic Profiling and Its Clinical Implementation in Advanced Prostate Cancer.

Ivana Bratic Hench¹, Luca Roma¹, Floriana Conticelli^1,2

¹Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.

|January 11, 2024

Summary

This study shows targeted next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) can detect key prostate cancer (PCa) mutations. This liquid biopsy approach aids in guiding personalized treatment for advanced prostate cancer.

Keywords:

circulating cell-free DNA liquid biopsy next-generation sequencing precision medicine prostate cancer

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Area of Science:

Oncology
Genetics
Molecular Diagnostics

Background:

Prostate cancer (PCa) frequently progresses to metastatic disease, posing treatment challenges.
Lack of biomarkers for advanced PCa hinders personalized treatment sequencing.
Liquid biopsies offer a non-invasive method for molecular profiling.

Purpose of the Study:

To evaluate the diagnostic utility of a custom-targeted next-generation sequencing (NGS) panel.
To assess the potential of liquid biopsies in guiding personalized treatment for PCa.
To detect circulating tumor DNA (ctDNA) somatic mutations in metastatic PCa.

Main Methods:

Ultra-deep sequencing of plasma circulating free DNA (cfDNA) using a custom AmpliSeq HD NGS panel.
Analysis of samples from 40 metastatic castration-resistant PCa (mCRPC) and 28 metastatic hormone-naive PCa (mCSPC) patients.
Comparison of cfDNA mutations with matched primary tumor tissue in a subset of patients.

Main Results:

Somatic mutations were detected in cfDNA of 71% (48/68) of patients.
Tumor-derived mutations were identified in cfDNA of 50% (21/42) of patients with matched samples.
AR amplifications were found in 31% (12/39) of mCRPC patients.

Conclusions:

Targeted NGS of cfDNA demonstrates high sensitivity and specificity for detecting clinically relevant PCa mutations.
Liquid biopsies using this NGS approach show promise for guiding personalized treatment strategies in advanced PCa.
The method is particularly effective in detecting mutations in metastatic castration-resistant prostate cancer.