TY - JOUR
T1 - HIST1H2BB and MAGI2 methylation and somatic mutations as precision medicine biomarkers for diagnosis and prognosis of high-grade serous ovarian cancer
AU - Valle, Blanca L.
AU - Rodriguez-Torres, Sebastian
AU - Kuhn, Elisabetta
AU - Diaz-Montes, Teresa Delp
AU - Parrilla-Castellar, Edgardo
AU - Lawson, Fahcina P.
AU - Folawiyo, Oluwasina
AU - Ili-Gangas, Carmen
AU - Brebi-Mieville, Priscilla
AU - Eshleman, James R.
AU - Herman, James
AU - Shih, Ie Ming
AU - Sidransky, David
AU - Guerrero-Preston, Rafael
N1 - Funding Information:
This research was supported by HERA Ovarian Cancer Foundation Outside the Box Grant (to B.L. Valle); Ovarian Cancer Research Alliance (to I.-M. Shih); National Cancer Institute U01CA84986 (to D. Sidransky) and K01CA164092 (to R. Guerrero-Preston); P50CA228991 (to I.-M. Shih) and National Institute on Minority Health and Health Disparities R44MD014911 (to R. Guerrero-Preston).
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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 ¼ 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 ¼ 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.
AB - 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 ¼ 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 ¼ 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.
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U2 - 10.1158/1940-6207.CAPR-19-0412
DO - 10.1158/1940-6207.CAPR-19-0412
M3 - Article
C2 - 32581010
AN - SCOPUS:85100486746
SN - 1940-6207
VL - 13
SP - 783
EP - 794
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 9
ER -