PMID- 32581010
OWN - NLM
STAT- MEDLINE
DCOM- 20211101
LR  - 20211230
IS  - 1940-6215 (Electronic)
IS  - 1940-6207 (Print)
IS  - 1940-6215 (Linking)
VI  - 13
IP  - 9
DP  - 2020 Sep
TI  - HIST1H2BB and MAGI2 Methylation and Somatic Mutations as Precision Medicine 
      Biomarkers for Diagnosis and Prognosis of High-grade Serous Ovarian Cancer.
PG  - 783-794
LID - 10.1158/1940-6207.CAPR-19-0412 [doi]
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 = 
      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.
CI  - (c)2020 American Association for Cancer Research.
FAU - Valle, Blanca L
AU  - Valle BL
AD  - Otolaryngology Department, Head and Neck Cancer Research Division, The Johns 
      Hopkins University, School of Medicine, Baltimore, Maryland.
FAU - Rodriguez-Torres, Sebastian
AU  - Rodriguez-Torres S
AUID- ORCID: 0000-0003-1264-0497
AD  - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, 
      Massachusetts.
AD  - Department of Medicine, University of Pittsburgh, School of Medicine, Pittsburgh, 
      Pennsylvania.
FAU - Kuhn, Elisabetta
AU  - Kuhn E
AD  - Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore 
      Policlinico; Department of Biomedical, Surgical, and Dental Sciences, University 
      of Milan, Italy.
AD  - Departments of Pathology, Gynecology and Obstetrics, The Johns Hopkins 
      University, School of Medicine, Baltimore, Maryland.
FAU - Diaz-Montes, Teresa
AU  - Diaz-Montes T
AD  - The Lya Segall Ovarian Cancer Institute, Mercy Medical Center, Baltimore, 
      Maryland.
FAU - Parrilla-Castellar, Edgardo
AU  - Parrilla-Castellar E
AD  - Department of Pathology, University of Washington, Seattle, Washington.
FAU - Lawson, Fahcina P
AU  - Lawson FP
AD  - Otolaryngology Department, Head and Neck Cancer Research Division, The Johns 
      Hopkins University, School of Medicine, Baltimore, Maryland.
FAU - Folawiyo, Oluwasina
AU  - Folawiyo O
AD  - Otolaryngology Department, Head and Neck Cancer Research Division, The Johns 
      Hopkins University, School of Medicine, Baltimore, Maryland.
FAU - Ili-Gangas, Carmen
AU  - Ili-Gangas C
AUID- ORCID: 0000-0002-4009-4406
AD  - Laboratory Integrative Biology (LIBi), Center for Excellence in Translational 
      Medicine-Scientific and Technological Bioresources Nucleus (CEMT-BIOREN), 
      Universidad de La Frontera, Temuco, Chile.
FAU - Brebi-Mieville, Priscilla
AU  - Brebi-Mieville P
AD  - Laboratory Integrative Biology (LIBi), Center for Excellence in Translational 
      Medicine-Scientific and Technological Bioresources Nucleus (CEMT-BIOREN), 
      Universidad de La Frontera, Temuco, Chile.
FAU - Eshleman, James R
AU  - Eshleman JR
AD  - Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, 
      Maryland.
FAU - Herman, James
AU  - Herman J
AD  - Department of Medicine, University of Pittsburgh, School of Medicine, Pittsburgh, 
      Pennsylvania.
FAU - Shih, Ie-Ming
AU  - Shih IM
AD  - Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore 
      Policlinico; Department of Biomedical, Surgical, and Dental Sciences, University 
      of Milan, Italy.
FAU - Sidransky, David
AU  - Sidransky D
AD  - Otolaryngology Department, Head and Neck Cancer Research Division, The Johns 
      Hopkins University, School of Medicine, Baltimore, Maryland.
FAU - Guerrero-Preston, Rafael
AU  - Guerrero-Preston R
AD  - Otolaryngology Department, Head and Neck Cancer Research Division, The Johns 
      Hopkins University, School of Medicine, Baltimore, Maryland. 
      rafael.guerrero@upr.edu.
AD  - University of Puerto Rico School of Medicine, Department of Obstetrics and 
      Gynecology, San Juan, Puerto Rico.
AD  - LifeGene Biomarks Inc., San Juan, Puerto Rico.
LA  - eng
GR  - K01 CA164092/CA/NCI NIH HHS/United States
GR  - P50 CA228991/CA/NCI NIH HHS/United States
GR  - R44 MD014911/MD/NIMHD NIH HHS/United States
GR  - U01 CA084986/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200624
PL  - United States
TA  - Cancer Prev Res (Phila)
JT  - Cancer prevention research (Philadelphia, Pa.)
JID - 101479409
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (H2BC3 protein, human)
RN  - 0 (Histones)
RN  - 0 (Hydroxamic Acids)
RN  - 3X2S926L3Z (trichostatin A)
RN  - 776B62CQ27 (Decitabine)
RN  - EC 2.7.4.8 (Guanylate Kinases)
RN  - EC 2.7.4.8 (MAGI2 protein, human)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*genetics
MH  - Biomarkers, Tumor/*genetics
MH  - Cell Line, Tumor
MH  - Cohort Studies
MH  - Cystadenocarcinoma, Serous/*diagnosis/drug therapy/genetics/mortality
MH  - DNA Methylation/drug effects
MH  - Decitabine/pharmacology/therapeutic use
MH  - Down-Regulation
MH  - Epithelium
MH  - Fallopian Tubes/pathology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Guanylate Kinases/*genetics
MH  - Histones/*genetics
MH  - Humans
MH  - Hydroxamic Acids/pharmacology/therapeutic use
MH  - Mutation
MH  - Ovarian Neoplasms/*diagnosis/drug therapy/genetics/mortality
MH  - Ovary/pathology
MH  - Precision Medicine/methods
MH  - Promoter Regions, Genetic
MH  - Survival Analysis
PMC - PMC8082233
MID - NIHMS1605413
COIS- Conflicts of Interests: There are no conflicts of interests
EDAT- 2020/06/26 06:00
MHDA- 2021/11/03 06:00
PMCR- 2021/04/29
CRDT- 2020/06/26 06:00
PHST- 2019/08/29 00:00 [received]
PHST- 2020/04/15 00:00 [revised]
PHST- 2020/06/11 00:00 [accepted]
PHST- 2020/06/26 06:00 [pubmed]
PHST- 2021/11/03 06:00 [medline]
PHST- 2020/06/26 06:00 [entrez]
PHST- 2021/04/29 00:00 [pmc-release]
AID - 1940-6207.CAPR-19-0412 [pii]
AID - 10.1158/1940-6207.CAPR-19-0412 [doi]
PST - ppublish
SO  - Cancer Prev Res (Phila). 2020 Sep;13(9):783-794. doi: 
      10.1158/1940-6207.CAPR-19-0412. Epub 2020 Jun 24.