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| Status |
Public on Jan 01, 2018 |
| Title |
Identification and validation of a novel 3-gene methylation classifier for HPV-based cervical screening on self-samples |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
Background: Offering self-sampling of cervico-vaginal material for human papillomavirus (HPV) testing is an effective method to increase the coverage in cervical screening programmes. Molecular triage directly on HPV-positive self-samples for colposcopy referral opens the way to full molecular cervical screening. Here, we set out to identify a methylation classifier for detection of precancer (CIN3) or cancer, applicable to self-samples obtained by different devices. Findings: Genome-wide DNA methylation profiling of HPV-positive self-samples revealed 12 methylation targets for CIN3 detection. Multiplex quantitative methylation-specific PCR of these targets yielded a 3-gene methylation classifier (ASCL1, LHX8 and ST6GALNAC5), showing a very good clinical performance for CIN3 detection in both lavage (AUC=0.88; sensitivity=74%; specificity=79%) and brush (AUC=0.90; sensitivity=88%; specificity=81%) self-samples in the validation set. All self-samples from women with cervical cancer scored methylation-positive. Conclusion: By genome-wide DNA methylation profiling on self-samples, we identified a highly effective 3-gene methylation classifier for direct triage on self-samples from HPV-positive women.
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| Overall design |
68 self-sampled cervico-vaginal specimens were analysed by Illumina Infinium HumanMethylation450 BeadChip. This series comprised 28 HPV-positive controls, 36 from women with a CIN3 (precancer) and 4 from women with cervical squamous cell carcinoma.
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| Contributor(s) |
Verlaat W, Snoek BC, Heideman DA, Wilting SM, Snijders PJ, Novianti PW, van Splunter AP, Peeters CF, van Trommel NE, Massuger LF, Bekkers RL, Melchers WJ, van Kemenade FJ, Berkhof J, van de Wiel MA, Meijer CJ, Steenbergen RD |
| Citation(s) |
29632006 |
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| Submission date |
May 31, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Daoud Sie |
| E-mail(s) |
d.sie@vumc.nl
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| Phone |
+31 20 4442428
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| Organization name |
Vrije Universiteit Medical Center
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| Department |
Pathology
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| Lab |
Microarray Core Facility
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| Street address |
De Boelelaan 1117
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| City |
Amsterdam |
| ZIP/Postal code |
1081 HV |
| Country |
Netherlands |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (68)
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| Relations |
| BioProject |
PRJNA388677 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE99511_RAW.tar |
739.3 Mb |
(http)(custom) |
TAR (of IDAT) |
| Processed data included within Sample table |
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