Methylomic Landscapes of Ovarian Cancer Precursor Lesions
| Autor: | Yeh Wang, Thomas R. Pisanic, Ie Ming Shih, Tza-Huei Wang, Tian Li Wang, Hanru Sun, Michael Considine, Lihong Li |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
0301 basic medicine Cancer Research Biology 03 medical and health sciences 0302 clinical medicine Ovarian carcinoma Biomarkers Tumor medicine Fallopian Tube Neoplasms Humans Aged Retrospective Studies Ovarian Neoplasms Serous Tubal Intraepithelial Carcinoma Methylation DNA Methylation Middle Aged Prognosis medicine.disease Cystadenocarcinoma Serous Gene Expression Regulation Neoplastic Serous fluid 030104 developmental biology Differentially methylated regions medicine.anatomical_structure Oncology Case-Control Studies 030220 oncology & carcinogenesis DNA methylation Cancer research Female Ovarian cancer Precancerous Conditions Follow-Up Studies Fallopian tube |
| Zdroj: | Clinical Cancer Research. 26:6310-6320 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-20-0270 |
| Popis: | Purpose: The current paradigm in the development of high-grade serous ovarian carcinoma (HGSC) proposes that the majority of HGSCs arise from precursor serous tubal intraepithelial carcinoma (STIC) lesions of the fallopian tube. Here we survey genome-wide methylation in HGSC precursor lesions to identify genomic regions that exhibit high-specificity differential hypermethylation for potential use as biomarkers for detecting STIC and HGSC at stages when curative intervention likely remains feasible. Experimental Design: We first identified quality control criteria for performing reliable methylomic analysis of DNA-limited tubal precursor lesions with the Illumina Infinium MethylationEPIC array. We then used this platform to compare genome-wide methylation among 12 STICs with paired adjacent-normal epithelia, one p53 signature lesion and two samples of concurrent HGSC. The resulting methylomic data were analyzed by unsupervised hierarchical clustering and multidimensional analysis. Regions of high-confidence STIC-specific differential hypermethylation were identified using selective bioinformatic criteria and compared with published MethylationEPIC data from 23 HGSC tumors and 11 healthy fallopian tube mucosae. Results: Unsupervised analysis showed that STICs largely clustered with HGSCs, but were clearly distinct from adjacent-normal fallopian tube epithelia. Forty-two genomic regions exhibited high-confidence STIC-specific differential hypermethylation, of which 17 (40.5%) directly overlapped with HGSC-specific differentially methylated regions. Methylation at these shared loci was able to completely distinguish STIC and HGSC samples from normal and adjacent-normal specimens. Conclusions: Our results suggest that most STICs are epigenetically similar to HGSCs and share regions of differential hypermethylation that warrant further evaluation for potential use as biomarkers for early detection of ovarian HGSC. See related commentary by Ishak and De Carvalho, p. 6083 |
| Databáze: | OpenAIRE |
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