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Targeted Sequencing of Human Satellite 2 Repeat Sequences in Plasma cfDNA Reveals Potential Breast Cancer Biomarkers. | LitMetric

Targeted Sequencing of Human Satellite 2 Repeat Sequences in Plasma cfDNA Reveals Potential Breast Cancer Biomarkers.

Diagnostics (Basel)

Munich Biomarker Research Center, Institute of Laboratory Medicine, German Heart Center, Technical University Munich, 80636 Munich, Germany.

Published: March 2024

AI Article Synopsis

  • Liquid biopsies are changing the way we detect and manage cancer by analyzing cell-free DNA (cfDNA) for potential biomarkers, like human satellite 2 (HSATII), which shows elevated levels in cancer patients.
  • This study focused on comparing HSATII levels in the plasma of breast cancer patients to healthy individuals using targeted sequencing and copy number variation (CNV) analysis.
  • Results indicated significant CNVs in HSATII sequences linked to breast cancer, while challenges with cfDNA fragmentation complicate data interpretation, highlighting the need for improved sequencing methods for cancer screening.

Article Abstract

Liquid biopsies are revolutionizing the detection and management of malignant diseases. While repetitive DNA sequences, such as LINE-1 and ALU are established in cell-free DNA (cfDNA) research, their clinical applications remain limited. In this study, we explore human satellite 2 (HSATII), a prevalent repeat DNA sequence in plasma that exhibits increased levels in cancer patients, thereby positioning it as a potential pan-cancer biomarker. We employed targeted sequencing and copy number variation (CNV) analysis using two primer pairs to assess the differential abundance of HSATII sequences in the plasma of breast cancer patients compared to healthy individuals. PCR amplicons of HSATII from 10 patients and 10 control subjects were sequenced, generating 151 bp paired-end reads. By constructing a pooled reference dataset, HSATII copy ratios were estimated in the patients. Our analysis revealed several significant CNVs in HSATII, with certain sequences displaying notable gains and losses across all breast cancer patients, suggesting their potential as biomarkers. However, we observed pronounced fragmentation of cfDNA in cancer, leading to the loss of longer PCR amplicons (>180 bp). While not all observed losses can be attributed to fragmentation artifacts, this phenomenon does introduce complexity in interpreting CNV data. Notably, this research marks the first instance of targeted HSATII sequencing in a liquid biopsy context. Our findings lay the groundwork for developing sequencing-based assays to detect differentially represented HSATII sequences, potentially advancing the field of minimally-invasive cancer screening.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10968943PMC
http://dx.doi.org/10.3390/diagnostics14060609DOI Listing

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