DNA Methylation Differences Associated with Tumor Tissues Identified by Genome Scanning Analysis

• Published in: Genomics (San Diego, Calif.) Calif.), 1998-11, Vol.53 (3), p.260-268
• Main Authors: Liang, Gangning, Salem, Carol E, Yu, Mimi C, Nguyen, Hung D, Gonzales, Felicidad A, Nguyen, TuDung T, Nichols, Peter W, Jones, Peter A
• Format: Article
• Language: English
• Subjects: Base Sequence; Biological and medical sciences; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; CpG Islands; DNA Methylation; DNA Primers - genetics; DNA, Neoplasm - blood; DNA, Neoplasm - genetics; DNA, Neoplasm - metabolism; Fundamental and applied biological sciences. Psychology; Genes, Tumor Suppressor; Genome, Human; Humans; Leukocytes - metabolism; Male; Molecular and cellular biology; Neoplasms - genetics; Neoplasms - metabolism; Phenotype; Polymerase Chain Reaction - methods; Promoter Regions, Genetic; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Transcription, Genetic; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1998.5502

Most investigations on the role of DNA methylation in cancer have focused on epigenetic changes associated with known tumor suppressor genes. This may have led to an underestimation of the number of CpG islands altered by DNA methylation, since it is possible that a subset of unknown genes relevant to cancer development may preferentially be affected by epigenetic rather than genetic means and would not be identified as familial deletions, mutations, or loss of heterozygosity. We used a recently developed screening procedure (methylation-sensitive arbitrarily primed-polymerase chain reaction to scan genomic DNA for CpG islands methylated in white blood cells (WBCs) and in tumor tissues. DNA methylation pattern analysis showed little interindividual differences in the WBCs and normal epithelium (adjacent to colon, bladder, and prostate cancer cells), but with some tissue-specific differences. Cancer cells showed marked methylation changes that varied considerably between different tumors, suggesting variable penetrance of the methylation phenotype in patients. Direct sequencing of 8 of 45 bands altered in these cancers showed that several of them were CpG islands, and 2 of these sequences were identified in GenBank. Surprisingly, three of the bands studied corresponded to transcribed regions of genes. Thus, hypermethylation of CpG islands in cancer cells is not confined to the promoters of growth regulatory genes but is also found in actively transcribed regions.