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Peer-reviewedCC BY 4.0Hereditary Cancer in Clinical Practice

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

  • Joonsang Yu1
  • Jaeyeon Ryu1
  • Sollip Kim1
  • Jihun Kim2
  • Yong Sang Hong3
  • Woochang Lee1
  • Seok-Byung Lim4
  • Jeong-Sik Byeon5
  • Sail Chun1
5 affiliations
  1. 1Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
  2. 2Department of Pathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
  3. 3Department of Oncology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
  4. 4Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
  5. 5Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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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.

Methods: 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.

Results: 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.

Conclusion: 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.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13053-026-00350-1.

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Cite

BibTeXRIS
BibTeX
@article{yu2026panelbased,
  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}},
  author = {Joonsang Yu and Jaeyeon Ryu and Sollip Kim and Jihun Kim and Yong Sang Hong and Woochang Lee and Seok-Byung Lim and Jeong-Sik Byeon and Sail Chun},
  journal = {Hereditary Cancer in Clinical Practice},
  year = {2026},
  month = aug,
  doi = {10.1186/s13053-026-00350-1},
  url = {https://doi.org/10.1186/s13053-026-00350-1},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - 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
AU  - Joonsang Yu
AU  - Jaeyeon Ryu
AU  - Sollip Kim
AU  - Jihun Kim
AU  - Yong Sang Hong
AU  - Woochang Lee
AU  - Seok-Byung Lim
AU  - Jeong-Sik Byeon
AU  - Sail Chun
PY  - 2026
DA  - 2026/08/07
JO  - Hereditary Cancer in Clinical Practice
DO  - 10.1186/s13053-026-00350-1
UR  - https://doi.org/10.1186/s13053-026-00350-1
AB  - 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.  Methods: 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.  Results: 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.  Conclusion: 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.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13053-026-00350-1.
SN  - 1731-2302
SN  - 1897-4287
ER  -