Evaluating Liquid Biopsy for Circulating Tumor DNA (ctDNA) Detection as a Complementary Diagnostic Tool in Thyroid Cancer Among Ecuadorian Women

TL;DR

This study explores liquid biopsy for detecting tumor DNA in blood as a complementary diagnostic tool for thyroid cancer in Ecuadorian women.

Contribution

The study evaluates ctDNA concordance with tumor tissue in an Ecuadorian cohort, highlighting potential and challenges in admixed populations.

Findings

71 cancer-associated variants were detected with 81.69% concordance between ctDNA and tumor DNA.

TP53 was the most frequently mutated gene, and some variants were exclusive to ctDNA, indicating tumor heterogeneity.

Ancestry analysis showed a predominant Native American genetic component in the Ecuadorian cohort.

Abstract

Thyroid cancer (TC) is the most common endocrine malignancy, with a rising global incidence. In Ecuador, TC rates are among the highest worldwide. Generally, fine-needle aspiration (FNA) remains the standard diagnostic tool; however, due to its limitations, alternative or complementary approaches are required. In this context, liquid biopsy, particularly circulating tumor DNA (ctDNA), offers a promising, minimally invasive option for tumor genotyping. Objective: This study evaluated the concordance between genetic variants identified in ctDNA and tumor tissue. Thirty-six women with papillary thyroid cancer were included. Tumor tissue and blood samples were collected, and DNA was extracted. Next-Generation Sequencing (NGS) using the TruSight Tumor 15 panel identified genetic variants in both ctDNA and tumor DNA. Variant pathogenicity was assessed following ACMG guidelines. Genetic ancestry was determined using Ancestry Informative Markers (AIMs). A total of 71 cancer-associated variants were detected, with 81.69% concordance between tumor DNA and ctDNA. TP53 was the most frequently mutated gene. While most pathogenic variants were found in tumor tissue, some variants appeared exclusively in ctDNA samples on specific patients, suggesting tumor heterogeneity. Ancestry analysis revealed a predominant Native American component (62.4%). Liquid biopsy demonstrates high concordance with tumor tissue analysis and holds potential as a complementary diagnostic tool for thyroid cancer. However, challenges such as low ctDNA yield and underrepresentation in genetic databases highlight the need for improved protocols and increased inclusion of admixed populations in genomic studies.

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