title: Human Colorectal Cancer Stage-dependent Global DNA Hypomethylation of Cancer-associated Fibroblasts.
abstract: Cancer-associated fibroblasts (CAFs) play an important role in tumor development and progression. The prevailing consensus favors the view that a specific epigenetic signature underpins the stable CAF phenotype. The aim of the present study was to assess global DNA methylation in CAFs during the adenoma-carcinoma sequence in non-familial sporadic human colorectal cancer (CRC).
  
  
  
  Immunohistochemical staining of nuclear 5-methylcytosine (5'-meCyt) was performed in matched samples of colonic tumor tissue and normal colonic mucosa excised from six patients with adenomas and four with adenocarcinomas. The staining intensity was expressed semi-quantitatively as the immunohistochemical staining score (ISS).
  
  
  
  ISS values of human colonic CAFs and adenomatous samples were 14.00±2.2 and 14.08±1.8, respectively, showing no statistically significant difference. In contrast, a marked trend was found towards global DNA hypomethylation in CAFs from adenocarcinomatous specimens compared to matched normal mucosa: ISS: 9.25±2.44 (range=6-11) vs. 16.17±0.75, respectively, p<0.03.
  
  
  
  Final stages of cancer development in CRC are associated with global DNA hypomethylation in stromal CAFs.
authors.affiliation: Pediatrics Department B, Saban Pediatric Medical Center for Israel, Soroka University Medical Center, Beer Sheva, Israel Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Eduard
authors.initials: E
authors.lastname: Ling
authors.affiliation: Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer Sheva, Israel Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer Sheva, Israel.
authors.forename: Amit
authors.initials: A
authors.lastname: Ringel
authors.affiliation: Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer Sheva, Israel Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer Sheva, Israel.
authors.forename: Ina
authors.initials: I
authors.lastname: Sigal-Batikoff
authors.affiliation: Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer Sheva, Israel.
authors.forename: Naim
authors.initials: N
authors.lastname: Abu-Freha
authors.affiliation: Institute of Pathology, Wolfson Medical Center, Holon, Israel.
authors.forename: Hananya
authors.initials: H
authors.lastname: Vaknine
authors.affiliation: Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer Sheva, Israel.
authors.forename: Wledy
authors.initials: W
authors.lastname: Friah
authors.affiliation: Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Surgery Department B, Soroka University Medical Center, Beer Sheva, Israel.
authors.forename: Avraham
authors.initials: A
authors.lastname: Reshef
authors.affiliation: Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Unit of Colorectal Surgery, Soroka University Medical Center, Beer Sheva, Israel.
authors.forename: Ilia
authors.initials: I
authors.lastname: Pinsk
authors.affiliation: Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer Sheva, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Fich
authors.affiliation: Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer Sheva, Israel Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Beer Sheva, Israel sergiol@bgu.ac.il.
authors.forename: Sergio
authors.initials: S
authors.lastname: Lamprecht
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000236:Adenoma / Q000196:embryology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D010641:Phenotype
chemical_list: D014408:Biomarkers, Tumor
keywords: Methylation; colorectal cancer; fibroblasts