Identification of Tissue of Origin in Cancer of Unknown Primary using a Targeted Bisulfite Sequencing Panel

Abstract

Aim: To construct a targeted bisulfite sequencing panel predicting origin of cancer of unknown primary. Methods: A bisulfite sequencing panel targeting 2793 tissue-specific markers was performed in 100 clinical samples. Results: The authors’ prediction model showed 0.85 accuracy for the ‘first-ranked’ tissue type and 0.93 accuracy for the ‘second-ranked’ tissue type using 2793 tissue-specific markers and 0.84 accuracy for the ‘first-ranked’ tissue type and 0.92 accuracy for the ‘second-ranked’ tissue type when the number of tissue-specific markers was reduced to 514. Conclusion: Targeted bisulfite sequencing is a useful method for predicting the tissue of origin in patients with cancer of unknown primary.

Plain language summary

When patients with cancer present with tumors that have migrated from elsewhere in the body, it is difficult for clinicians to identify where the cancer originated. DNA methylation profiling is a promising test to help identify where the cancer originated because it reflects cell of origin and is compatible with formalin-fixed, paraffin-embedded tissues. Because next-generation sequencing has already been implemented in clinical laboratories, the authors developed a targeted bisulfite sequencing panel that could predict the tissue of origin using genomic DNA extracted from formalin-fixed, paraffin-embedded tissues. The authors found that a hybrid capture-based targeted bisulfite sequencing panel is a useful method for predicting the tissue of origin in patients with cancer of unknown primary origin in clinical practice.

Graphical abstract

Keywords::

• bisulfite sequencing
• cancer of unknown primary
• methylation
• prediction model
• tissue of origin

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2021-0477

Author contributions

JM Bae, K Kim and GH Kang conceived and designed the study. JM Bae and JY Ahn developed the methodology and wrote, reviewed and revised the manuscript. JM Bae, JY Ahn and H Lee acquired, analyzed and interpreted the data and performed statistical analysis. H Jang, H Han, J Jeong and N-Y Cho provided technical and material support. All authors read and approved the final manuscript.

Financial&competing interests disclosure

This study was supported by grants from the National Research Foundation funded by the Korean Ministry of Education (NRF-2017R1D1A1B0303007) and the Seoul National University Hospital Research Fund (03-2016-0090). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that all samples derived from the Seoul National University Hospital Cancer Tissue Bank, Seoul, Korea, were obtained with informed consent and the study was approved by the institutional review board of Seoul National University Hospital (H-1703-139-840).

Data availability statement

The dataset used and analyzed in the current study is available from the corresponding author upon reasonable request. The source codes used in this study are provided as supplementary material.

Additional information

Funding

This study was supported by grants from the National Research Foundation funded by the Korean Ministry of Education (NRF-2017R1D1A1B0303007) and the Seoul National University Hospital Research Fund (03-2016-0090). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.