Circulating tumour-derived DNA in metastatic soft tissue sarcoma.

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Soft tissue sarcoma (STS) has a high recurrence rate (40%) after treatment.
• Circulating cell-free DNA (cfDNA) and circulating tumor-derived DNA (ctDNA) show promise as biomarkers in other cancers.
• Limited data exists on cfDNA/ctDNA in STS patients.

Purpose of the Study:

• To genetically characterize plasma cfDNA and ctDNA in metastatic STS patients.
• To assess the correlation between cfDNA levels and disease burden.
• To identify potential ctDNA mutations and genetic alterations in STS.

Main Methods:

• Utilized a custom Ion AmpliSeq™ panel for genetic characterization.
• Analyzed plasma cfDNA, buffy coat (germline) DNA, and FFPE primary STS tissue DNA.
• Included a cohort of 11 metastatic STS patients.

Main Results:

• Total cfDNA levels were significantly elevated in STS patients.
• ctDNA was detected in 36% (4/11) of patients across various STS subtypes and disease burdens.
• Cancer-associated mutations (TP53/PIK3CA) and allelic loss of heterozygosity were identified.

Conclusions:

• This is the largest study characterizing STS cfDNA/ctDNA to date.
• The findings support cfDNA/ctDNA as promising sources for novel STS biomarkers.
• Further research is needed to explore subtype-specific characteristics and clinical utility.