%0 Journal Article
%T Gene methylation profiles of normal mucosa, and benign and malignant colorectal tumors identify early onset markers
%A Terje Ahlquist
%A Guro E Lind
%A Vera L Costa
%A Gunn I Meling
%A Morten Vatn
%A Geir S Hoff
%A Torleiv O Rognum
%A Rolf I Skotheim
%A Espen Thiis-Evensen
%A Ragnhild A Lothe
%J Molecular Cancer
%D 2008
%I BioMed Central
%R 10.1186/1476-4598-7-94
%X The methylation status of eleven genes (ADAMTS1, CDKN2A, CRABP1, HOXA9, MAL, MGMT, MLH1, NR3C1, PTEN, RUNX3, and SCGB3A1) was determined in 154 tissue samples including normal mucosa, adenomas, and carcinomas of the colorectum. The gene-specific and widespread methylation status among the carcinomas was related to patient gender and age, and microsatellite instability status. Possible CIMP tumors were identified by comparing the methylation profile with microsatellite instability (MSI), BRAF-, KRAS-, and TP53 mutation status.The mean number of methylated genes per sample was 0.4 in normal colon mucosa from tumor-free individuals, 1.2 in mucosa from cancerous bowels, 2.2 in adenomas, and 3.9 in carcinomas. Widespread methylation was found in both adenomas and carcinomas. The promoters of ADAMTS1, MAL, and MGMT were frequently methylated in benign samples as well as in malignant tumors, independent of microsatellite instability. In contrast, normal mucosa samples taken from bowels without tumor were rarely methylated for the same genes. Hypermethylated CRABP1, MLH1, NR3C1, RUNX3, and SCGB3A1 were shown to be identifiers of carcinomas with microsatellite instability. In agreement with the CIMP concept, MSI and mutated BRAF were associated with samples harboring hypermethylation of several target genes.Methylated ADAMTS1, MGMT, and MAL are suitable as markers for early tumor detection.Most cases of colorectal cancer (CRC) originate from adenomas. The malignant potential of adenomas increases with size, grade of dysplasia, and degree of villous components,[1] along with the number and order of genetic and epigenetic aberrations.[2] The majority (~85%) of the sporadic carcinomas are characterized by chromosomal aberrations, referred to as a chromosomal unstable (CIN) phenotype, whereas the smaller group (~15%) typically show microsatellite instability (MSI) caused by defect DNA mismatch repair.[2] Most CIN tumors are microsatellite stable (MSS). A third molecular phenotyp
%U http://www.molecular-cancer.com/content/7/1/94