title: SEPT9andSHOX2DNA methylation status and its utility in the diagnosis of colonic adenomas and colorectal adenocarcinomas.
abstract: Colorectal cancer (CRC) appear to arise from precursor lesions in a well-characterized adenoma-carcinoma sequence. Significant efforts have been invested to develop biomarkers that identify early adenocarcinomas and adenomas with high-grade dysplasia, since these are believed to harbor a particularly high risk for malignant transition and thus require resection. Promoter methylation ofSEPT9andSHOX2has been suggested as a biomarker for various solid malignant tumors. Hence, the present study aimed to test their biomarker potential in CRC and precursor lesions.
  
  
  
  Assessment of promoter methylation ofSEPT9distinguished adenomas and CRC from controls as well as advanced from non-advanced adenomas (allp< 0.001). Correspondingly,SHOX2methylation levels in adenomas and colorectal carcinomas were significantly higher compared to those in normal control tissues (p< 0.001). Histologic transition from adenomas to CRC was paralleled by amplification of theSEPT9gene locus.
  
  
  
  SEPT9/SHOX2methylation assays may help to distinguish colorectal cancer and adenomas from normal and inflammatory colonic tissue, as well as advanced from non-advanced adenomas. Further studies need to validate these findings before introduction in clinical routine.
authors.affiliation: Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Alexander
authors.identifier: 0000-0001-5424-3217
authors.initials: A
authors.lastname: Semaan
authors.affiliation: Institute of Pathology, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: van Ellen
authors.affiliation: Institute of Pathology, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Meller
authors.affiliation: Institute of Pathology, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Bergheim
authors.affiliation: Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Branchi
authors.affiliation: Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Lingohr
authors.affiliation: Institute of Pathology, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Diane
authors.initials: D
authors.lastname: Goltz
authors.affiliation: Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Kalff
authors.affiliation: Institute of Pathology, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Matthaei
authors.affiliation: Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pantelis
authors.affiliation: Institute of Pathology, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany.
authors.forename: Dimo
authors.initials: D
authors.lastname: Dietrich
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics; D000236:Adenoma / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics; D019175:DNA Methylation; D003937:Diagnosis, Differential; D055088:Early Detection of Cancer; D044127:Epigenesis, Genetic; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D058112:Septins / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C484664:SHOX2 protein, human; C474315:SEPTIN9 protein, human; D058112:Septins
keywords: Adenomas; Amplification; Colorectal cancer; Methylation; SEPT9; SHOX2