title: Proteomics of differential extraction fractions enriched for chromatin-binding proteins from colon adenoma and carcinoma tissues.
abstract: BACKGROUND
  Altered nuclear and genomic structure and function are hallmarks of cancer cells. Research into nuclear proteins in human tissues could uncover novel molecular processes in cancer. Here, we examine biochemical tissue fractions containing chromatin-binding (CB) proteins in the context of colorectal cancer (CRC) progression.
  
  
  METHODS
  CB protein-containing fractions were biochemically extracted from human colorectal tissues, including carcinomas with chromosomal instability (CIN), carcinomas with microsatellite instability (MIN), and adenomas. The CB proteins were subjected to label-free LC-MS/MS and the data were analyzed by bioinformatics.
  
  
  RESULTS
  Over 1700 proteins were identified in the CB fraction from colonic tissues, including 938 proteins associated with nuclear annotation. Of the latter, 169 proteins were differential between adenomas and carcinomas. In this adenoma-versus-carcinoma comparison, apart from specific changes in components of the splicing and protein translational machineries, we also identified significant changes in several proteins associated with chromatin-directed functions. Furthermore, several key cell cycle proteins as well as those involved in cellular stress were increased, whereas specific components of chromosome segregation and DNA recombination/repair systems were decreased.
  
  
  CONCLUSIONS
  Our study identifies proteomic changes at the subnuclear level that are associated with CRC and may be further investigated. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.
authors.affiliation: OncoProteomics Laboratory, Dept. of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Jaco C
authors.initials: JC
authors.lastname: Knol
authors.affiliation: OncoProteomics Laboratory, Dept. of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Meike
authors.initials: M
authors.lastname: de Wit
authors.affiliation: OncoProteomics Laboratory, Dept. of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands; Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Albrethsen
authors.affiliation: OncoProteomics Laboratory, Dept. of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Sander R
authors.initials: SR
authors.lastname: Piersma
authors.affiliation: OncoProteomics Laboratory, Dept. of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Thang V
authors.initials: TV
authors.lastname: Pham
authors.affiliation: Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: Mongera
authors.affiliation: Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Carvalho
authors.affiliation: Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Remond J A
authors.initials: RJ
authors.lastname: Fijneman
authors.affiliation: Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands.
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.affiliation: OncoProteomics Laboratory, Dept. of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands. Electronic address: c.jimenez@vumc.nl.
authors.forename: Connie R
authors.initials: CR
authors.lastname: Jiménez
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D002853:Chromatography, Liquid; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D063990:Gene Ontology; D006801:Humans; D053842:Microsatellite Instability; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D013347:Subcellular Fractions; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D002843:Chromatin; D009363:Neoplasm Proteins; D009687:Nuclear Proteins
keywords: Adenoma; Cancer tissue; Carcinoma; Chromatin-binding; Colorectal; Proteomics