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Cell-Free DNA Methylation of Selected Genes Allows for Early Detection of the Major Cancers in Women

1
Cancer Biology & Epigenetics Group—Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal
2
Master in Oncology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
3
Breast Cancer Clinic and Department of Medical Oncology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal
4
Lung Cancer Clinic and Department of Medical Oncology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal
5
Digestive Tract Pathology Clinic and Surgical Oncology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal
6
Department of Epidemiology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal
7
Department of Pathology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal
8
Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
*
Author to whom correspondence should be addressed.
Cancers 2018, 10(10), 357; https://doi.org/10.3390/cancers10100357
Received: 24 August 2018 / Revised: 21 September 2018 / Accepted: 25 September 2018 / Published: 26 September 2018
(This article belongs to the Special Issue Cancer Biomarkers)
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PDF [1492 KB, uploaded 26 September 2018]
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Abstract

Background: Breast (BrC), colorectal (CRC) and lung (LC) cancers are the three most common and deadly cancers in women. Cancer screening entails an increase in early stage disease detection but is hampered by high false-positive rates and overdiagnosis/overtreatment. Aberrant DNA methylation occurs early in cancer and may be detected in circulating cell-free DNA (ccfDNA), constituting a valuable biomarker and enabling non-invasive testing for cancer detection. We aimed to develop a ccfDNA methylation-based test for simultaneous detection of BrC, CRC and LC. Methods: CcfDNA from BrC, CRC and LC patients and asymptomatic controls were extracted from plasma, sodium-bisulfite modified and whole-genome amplified. APC, FOXA1, MGMT, RARβ2, RASSF1A, SCGB3A1, SEPT9, SHOX2 and SOX17 promoter methylation levels were determined by multiplex quantitative methylation-specific PCR. Associations between methylation and standard clinicopathological parameters were assessed. Biomarkers’ diagnostic performance was also evaluated. Results: A “PanCancer” panel (APC, FOXA1, RASSF1A) detected the three major cancers with 72% sensitivity and 74% specificity, whereas a “CancerType” panel (SCGB3A1, SEPT9 and SOX17) indicated the most likely cancer topography, with over 80% specificity, although with limited sensitivity. Conclusions: CcfDNA’s methylation assessment allows for simultaneous screening of BrC, CRC and LC, complementing current modalities, perfecting cancer suspects’ triage, increasing compliance and cost-effectiveness. View Full-Text
Keywords: breast cancer; colorectal cancer; lung cancer; DNA methylation; epigenetic biomarker; cell-free DNA; liquid biopsy; detection breast cancer; colorectal cancer; lung cancer; DNA methylation; epigenetic biomarker; cell-free DNA; liquid biopsy; detection
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Nunes, S.P.; Moreira-Barbosa, C.; Salta, S.; Palma de Sousa, S.; Pousa, I.; Oliveira, J.; Soares, M.; Rego, L.; Dias, T.; Rodrigues, J.; Antunes, L.; Henrique, R.; Jerónimo, C. Cell-Free DNA Methylation of Selected Genes Allows for Early Detection of the Major Cancers in Women. Cancers 2018, 10, 357.

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