title: GHSR DNA hypermethylation is a common epigenetic alteration of high diagnostic value in a broad spectrum of cancers.
abstract: Identification of a single molecular trait that is determinant of common malignancies may serve as a powerful diagnostic supplement to cancer type-specific markers. Here, we report a DNA methylation mark that is characteristic of seven studied malignancies, namely cancers of lung, breast, prostate, pancreas, colorectum, glioblastoma and B cell chronic lymphocytic leukaemia (CLL) (n = 137). This mark was defined by substantial hypermethylation at the promoter and first exon of growth hormone secretagouge receptor (GHSR) through bisulfite pyrosequencing. The degree of aberrant methylation was capable of accurate discrimination between cancer and control samples. The highest sensitivity and specificity of cancer detection was achieved for cancers of pancreas, lung, breast and CLL yielding the area under the curve (AUC) values of 1.0000, 0.9952, 0.9800 and 0.9400, respectively. Narrowing to a single CpG site within the gene's promoter or four consecutive CpG units of the highest methylation levels within the first exon improved the detection power. GHSR hypermethylation was detected already at the early stage tumors. The accurate performance of this marker was further replicated in an independent set of pancreatic cancer and control samples (n = 78). These findings support the candidature of GHSR methylation as a highly accurate pan-cancer marker.
authors.affiliation: Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.|Diagnostic Molecular Pathology, Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Evgeny A
authors.initials: EA
authors.lastname: Moskalev
authors.affiliation: Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Pouria
authors.initials: P
authors.lastname: Jandaghi
authors.affiliation: Molecular Genetic Epidemiology, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Fallah
authors.affiliation: Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Manoochehri
authors.affiliation: Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Botla
authors.affiliation: Military Training Research Center, Zhukovsky - Gagarin Air Force Academy, Voronezh, Russia.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Kolychev
authors.affiliation: Molecular Haematology, National Research Centre for Haematology, Moscow, Russia.
authors.forename: Evgeny A
authors.initials: EA
authors.lastname: Nikitin
authors.affiliation: Department of Genomics and Immunology, Odessa State Medical University, Odessa, Ukraine.
authors.forename: Vladymyr V
authors.initials: VV
authors.lastname: Bubnov
authors.affiliation: Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: von Knebel Doeberitz
authors.affiliation: Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Strobel
authors.affiliation: Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Hackert
authors.affiliation: Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.affiliation: Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Nathalia
authors.initials: N
authors.lastname: Giese
authors.affiliation: Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bauer
authors.affiliation: Translational Research Unit, Thoraxklinik Heidelberg at Heidelberg University, Heidelberg, Germany.|Department of Translational Pneumology, Translational Lung Research Centre Heidelberg (TLRC-H), Member of the German Centre for Lung Research (DZL), Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Muley
authors.affiliation: Institute of Pathology, University Hospital, Heidelberg, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.affiliation: Institute of Pathology, University Hospital, Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.affiliation: Diagnostic Molecular Pathology, Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Haller
authors.affiliation: Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Hoheisel
authors.affiliation: Functional Genome Analysis, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.|Current address: Department of Human Genetics and McGill University and Genome Quebec Innovation Centre, Montreal, Quebec.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Riazalhosseini
mesh_terms: D000328:Adult; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012372:ROC Curve; D054440:Receptors, Ghrelin / Q000032:analysis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D054440:Receptors, Ghrelin