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HIST1H2BB and MAGI2 Methylation and Somatic Mutations as Precision Medicine Biomarkers for Diagnosis and Prognosis of High-grade Serous Ovarian Cancer.
- Source :
-
Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2020 Sep; Vol. 13 (9), pp. 783-794. Date of Electronic Publication: 2020 Jun 24. - Publication Year :
- 2020
-
Abstract
- Molecular alterations that contribute to long-term (LT) and short-term (ST) survival in ovarian high-grade serous carcinoma (HGSC) may be used as precision medicine biomarkers. DNA promoter methylation is an early event in tumorigenesis, which can be detected in blood and urine, making it a feasible companion biomarker to somatic mutations for early detection and targeted treatment workflows. We compared the methylation profile in 12 HGSC tissue samples to 30 fallopian tube epithelium samples, using the Infinium Human Methylation 450K Array. We also used 450K methylation arrays to compare methylation among HGSCs long-term survivors (more than 5 years) and short-term survivors (less than 3 years). We verified the array results using bisulfite sequencing and methylation-specific PCR (qMSP). in another cohort of HGSC patient samples ( n = 35). Immunoblot and clonogenic assays after pharmacologic unmasking show that HIST1H2BB and MAGI2 promoter methylation downregulates mRNA expression levels in ovarian cancer cells. We then used qMSP in paired tissue, ascites, plasma/serum, vaginal swabs, and urine from a third cohort of patients with HGSC cancer ( n = 85) to test the clinical potential of HIST1H2BB and MAGI2 in precision medicine workflows. We also performed next-generation exome sequencing of 50 frequently mutated in human cancer genes, using the Ion AmpliSeqCancer Hotspot Panel, to show that the somatic mutation profile found in tissue and plasma can be quantified in paired urine samples from patients with HGSC. Our results suggest that HIST1H2BB and MAGI2 have growth-suppressing roles and can be used as HGSC precision medicine biomarkers.<br /> (©2020 American Association for Cancer Research.)
- Subjects :
- Cell Line, Tumor
Cohort Studies
Cystadenocarcinoma, Serous drug therapy
Cystadenocarcinoma, Serous genetics
Cystadenocarcinoma, Serous mortality
DNA Methylation drug effects
Decitabine pharmacology
Decitabine therapeutic use
Down-Regulation
Epithelium
Fallopian Tubes pathology
Female
Gene Expression Regulation, Neoplastic drug effects
Humans
Hydroxamic Acids pharmacology
Hydroxamic Acids therapeutic use
Mutation
Ovarian Neoplasms drug therapy
Ovarian Neoplasms genetics
Ovarian Neoplasms mortality
Ovary pathology
Precision Medicine methods
Promoter Regions, Genetic
Survival Analysis
Adaptor Proteins, Signal Transducing genetics
Biomarkers, Tumor genetics
Cystadenocarcinoma, Serous diagnosis
Guanylate Kinases genetics
Histones genetics
Ovarian Neoplasms diagnosis
Subjects
Details
- Language :
- English
- ISSN :
- 1940-6215
- Volume :
- 13
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cancer prevention research (Philadelphia, Pa.)
- Publication Type :
- Academic Journal
- Accession number :
- 32581010
- Full Text :
- https://doi.org/10.1158/1940-6207.CAPR-19-0412