{
  "abstract": "Background: Hereditary colorectal cancer syndromes, such as Lynch syndrome and familial adenomatous polyposis, arise from pathogenic/likely pathogenic (P/LP) germline variants in DNA mismatch repair or tumor suppressor genes. Traditional Sanger sequencing could cover only phenotype-driven genes and cannot detect copy number variants (CNVs). Next-generation sequencing (NGS) enables simultaneous multi-gene analysis and CNV detection. In this study, we compared the results of phenotype-driven Sanger sequencing with those of panel-based NGS in patients suspected of having hereditary colorectal cancer syndromes at a single institution.\n\nMethods: Patients tested for hereditary colorectal cancer syndromes between 2008 and 2018 (Sanger) and 2019–2022 (NGS) were retrospectively analyzed. The NGS assay targeted 171 cancer predisposition genes, and CNVs were inferred by read-depth analysis and confirmed with multiplex ligation-dependent probe amplification. Detected variants were classified per ACMG/AMP 2015 guidelines. Microsatellite instability (MSI) and mismatch repair (MMR) immunohistochemistry (IHC) results were compared with molecular findings.\n\nResults: Among 423 patients (254 Sanger, 169 NGS), the detection rate of pathogenic or likely pathogenic variants was higher in NGS (55.0%) than Sanger sequencing (40.6%). NGS additionally identified 17 CNVs (18.1%) that were undetectable by Sanger sequencing and revealed incidental P/LP variants in other cancer-related genes. MSI and MMR IHC results showed strong concordance with molecular findings.\n\nConclusion: Panel-based NGS with CNV analysis was associated with a higher detection rate of clinically relevant variants than phenotype-driven Sanger sequencing in this single-institution cohort. These findings support the clinical utility of comprehensive germline testing for patients suspected of having hereditary colorectal cancer syndromes, particularly when CNV detection or simultaneous multi-gene analysis is required.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13053-026-00350-1.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea",
    "Department of Pathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea",
    "Department of Oncology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea",
    "Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea",
    "Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Joonsang Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jaeyeon Ryu"
    },
    {
      "affs": [
        0
      ],
      "name": "Sollip Kim"
    },
    {
      "affs": [
        1
      ],
      "name": "Jihun Kim"
    },
    {
      "affs": [
        2
      ],
      "name": "Yong Sang Hong"
    },
    {
      "affs": [
        0
      ],
      "name": "Woochang Lee"
    },
    {
      "affs": [
        3
      ],
      "name": "Seok-Byung Lim"
    },
    {
      "affs": [
        4
      ],
      "name": "Jeong-Sik Byeon"
    },
    {
      "affs": [
        0
      ],
      "name": "Sail Chun"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1jmetgn8855vx.bib",
  "cited_by": 0,
  "doi": "10.1186/s13053-026-00350-1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732859/",
  "id": "1jmetgn8855vx",
  "issns": [
    "1731-2302",
    "1897-4287"
  ],
  "landing_url": "https://doi.org/10.1186/s13053-026-00350-1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2734|Genetic factors in colorectal cancer"
    ]
  ],
  "openalex": "W7201881198",
  "pdf_url": null,
  "pmcid": "PMC13732859",
  "pmid": "42983841",
  "published": "2026-08-07",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/1jmetgn8855vx.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:45Z",
      "native_id": "PMC13732859",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s13053-026-00350-1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2734|Genetic factors in colorectal cancer",
      "subfield": "general"
    }
  ],
  "title": "Panel-based next-generation sequencing with copy number variant detection pipeline could increase the detection rate of hereditary colorectal cancer syndrome compared with Sanger sequencing",
  "title_text": "Panel-based next-generation sequencing with copy number variant detection pipeline could increase the detection rate of hereditary colorectal cancer syndrome compared with Sanger sequencing",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:45Z",
  "url": "https://research.draconitic.com/paper/1jmetgn8855vx",
  "venue": "Hereditary Cancer in Clinical Practice",
  "versions": []
}