Efficient mutation screening for cervical cancers from circulating tumor DNA in blood

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• Early diagnosis and continuous monitoring are crucial for effective cervical cancer (CC) management.
• Liquid biopsy using circulating tumor DNA (ctDNA) offers a non-invasive approach for cancer marker testing.
• Limited investigation exists on tumor-specific ctDNA alterations for CC diagnosis and monitoring.

Purpose of the Study:

• To develop and evaluate a Next-Generation Sequencing (NGS) panel for cervical cancer (CC) diagnosis and monitoring.
• To identify and characterize somatic variations in ctDNA for CC patients.
• To assess the utility of ctDNA alterations as biomarkers for treatment response.

Main Methods:

• A bioinformatics approach was used to design a 24-gene NGS panel for CC.
• The panel targets somatic single-nucleotide variations, indels, and copy number variations.
• ctDNA samples from 24 CC patients undergoing chemotherapy and radiotherapy were analyzed.

Main Results:

• Mutations were detected in 18 out of 24 genes within the NGS CC panel across all patients.
• Key mutated genes include ZFHX3 (83%), KMT2C (79%), KMT2D (79%), NSD1 (67%), ATM (38%), and RNF213 (27%).
• RNF213 mutations showed potential as a monitoring marker for chemo- and radiotherapy response.

Conclusions:

• The developed NGS CC panel is effective for diagnosing and monitoring cervical cancer.
• The panel successfully identified common somatic variations in CC patients.
• Observed changes in genetic variations correlate with patient treatment patterns, aiding in personalized monitoring.