title: NotI microarrays: novel epigenetic markers for early detection and prognosis of high grade serous ovarian cancer.
abstract: Chromosome 3-specific NotI microarray (NMA) containing 180 clones with 188 genes was used in the study to analyze 18 high grade serous ovarian cancer (HGSOC) samples and 7 benign ovarian tumors. We aimed to find novel methylation-dependent biomarkers for early detection and prognosis of HGSOC. Thirty five NotI markers showed frequency of methylation/deletion more or equal to 17%. To check the results of NMA hybridizations several samples for four genes (LRRC3B, THRB, ITGA9 and RBSP3 (CTDSPL)) were bisulfite sequenced and confirmed the results of NMA hybridization. A set of eight biomarkers: NKIRAS1/RPL15, THRB, RBPS3 (CTDSPL), IQSEC1, NBEAL2, ZIC4, LOC285205 and FOXP1, was identified as the most prominent set capable to detect both early and late stages of ovarian cancer. Sensitivity of this set is equal to (72 ± 11)% and specificity (94 ± 5)%. Early stages represented the most complicated cases for detection. To distinguish between Stages I + II and Stages III + IV of ovarian cancer the most perspective set of biomarkers would include LOC285205, CGGBP1, EPHB1 and NKIRAS1/RPL15. The sensitivity of the set is equal to (80 ± 13)% and the specificity is (88 ± 12)%. Using this technique we plan to validate this panel with new epithelial ovarian cancer samples and add markers from other chromosomes.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm SE-171 77, Sweden. eugene.zabarovsky@ki.se.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kashuba
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Dmitriev
authors.forename: George S
authors.initials: GS
authors.lastname: Krasnov
authors.forename: Tatiana
authors.initials: T
authors.lastname: Pavlova
authors.forename: Ilya
authors.initials: I
authors.lastname: Ignatjev
authors.forename: Vasily V
authors.initials: VV
authors.lastname: Gordiyuk
authors.forename: Anna V
authors.initials: AV
authors.lastname: Gerashchenko
authors.forename: Eleonora A
authors.initials: EA
authors.lastname: Braga
authors.forename: Surya P
authors.initials: SP
authors.lastname: Yenamandra
authors.forename: Michael
authors.initials: M
authors.lastname: Lerman
authors.forename: Vera N
authors.initials: VN
authors.lastname: Senchenko
authors.forename: Eugene
authors.initials: E
authors.lastname: Zabarovsky
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D006801:Humans; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D017422:Sequence Analysis, DNA
chemical_list: D014408:Biomarkers, Tumor; D015252:Deoxyribonucleases, Type II Site-Specific; C038565:GCGGCCGC-specific type II deoxyribonucleases