Combination of Hotspot Mutations With Methylation and Fragmentomic Profiles to Enhance Multi‐Cancer Early Detection
2025

Improving Early Cancer Detection with Hotspot Mutations

Sample size: 559 publication 10 minutes Evidence: high

Author Information

Author(s): Nguyen Thi Hue Hanh, Vu Giang Hoang, Nguyen Tu Thi, Nguyen Tuan Anh, Tran Vu Uyen, Vu Luyen Thi, Nguyen Giang Thi Huong, Nguyen Nhat Duy, Tran Trung Hieu, Nguyen Van Thien Chi, Nguyen Thanh Dat, Nguyen Trong Hieu, Vo Dac Ho, Van Thi Tuong Vi, Do Thanh Thi, Le Minh Phong, Huynh Le Anh Khoa, Nguyen Duy Sinh, Tang Hung Sang, Nguyen Hoai‐Nghia, Phan Minh‐Duy, Giang Hoa, Tu Lan N., Tran Le Son

Primary Institution: Medical Genetics Institute Ho Chi Minh Vietnam

Hypothesis

Can integrating hotspot mutations into the SPOT-MAS assay enhance early cancer detection rates?

Conclusion

Integrating genetic and epigenetic alterations into a multimodal assay significantly enhances the early detection of various cancers.

Supporting Evidence

  • Hotspot mutations were detected in 51.4% of cancer patients.
  • The highest detection rates were in liver cancer (96.5%).
  • Combining hotspot mutations with SPOT-MAS improved early-stage cancer detection to 78.5%.
  • SPOT-MAS showed higher sensitivity for early-stage cancers compared to hotspot mutations.

Takeaway

This study shows that combining different tests can help find cancer earlier, which is really important for treatment.

Methodology

A targeted amplicon sequencing approach was developed to profile 700 hotspot mutations in cell-free DNA and integrated into the SPOT-MAS assay, validated in a cohort of 255 cancer patients and 304 healthy individuals.

Potential Biases

Potential bias due to the retrospective nature and the absence of staging information for some patients.

Limitations

The study is retrospective and requires prospective validation in larger populations; also, the performance may be influenced by the amount and quality of cfDNA.

Participant Demographics

The study included 255 cancer patients (64 breast, 59 colorectal, 62 gastric, 29 liver, 41 lung) and 304 healthy individuals, with a median age of 50 years for controls.

Statistical Information

P-Value

p<0.0001

Confidence Interval

95% CI: 73.0–83.0

Statistical Significance

p<0.0001

Digital Object Identifier (DOI)

10.1002/cam4.70575

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