| | |  | | | | Record from Web of Science® | | | | | | |
| Analysis of Adenomatous Polyposis Coli promoter hypermethylation in human cancer |
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| Author(s): Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, Gonzalez S, Tarafa G, Sidransky D, Meltzer SJ, Baylin SB, Herman JG |
| Source: CANCER RESEARCH Volume: 60 Issue: 16 Pages: 4366-4371 Published: AUG 15 2000 |
| Times Cited: 276 References: 31 |
| Abstract: Germ-line mutations in the tumor suppressor gene APC are associated with hereditary familiar adenomatous polyposis (FAP), and somatic mutations are common in sporadic colorectal tumors. We now report that methylation in the promoter region of this gene constitutes an alternative mechanism for gene inactivation in colon and other tumors of the gastrointestinal tract. The.-IPC promoter is hypermethylated in 18% of primary sporadic colorectal carcinomas (n = 108) and adenoma (n = 48), and neoplasia with APC methylation fails to express the APC transcript. Methylation affects only wild-type APC in 95% of cases and is not observed in tumors from FAP patients who have germ-line APC mutations. As with APC mutation, aberrant APC methylation occurs early in colorectal carcinogenesis. When other tumor types are analyzed (n = 208), methylation of the APC promoter is not restricted to the colon but is present in tumors originating elsewhere in the gastrointestinal tract but rarely in other tumors. Our data suggest that hypermethylation of APC provides an important mechanism for impairing APC function and further underscores the importance of the APC pathway in gastrointestinal tumorigenesis. |
| Document Type: Article |
| Language: English |
| Reprint Address: Herman, JG (reprint author), Tumor Biol, Canc Res Bldg,1650 Orleans St, Baltimore, MD 21231 USA |
Addresses:
1. Johns Hopkins Oncol Ctr, Dept Oncol, Baltimore, MD 21231 USA
2. Johns Hopkins Oncol Ctr, Dept Otolaryngol Head & Neck Surg, Div Head & Neck Canc Res, Baltimore, MD 21231 USA
3. Inst Catala Oncol, Barcelona 08907, Spain
4. Inst Recerca Oncol, Barcelona 08907, Spain
5. Univ Maryland, Sch Med, Greenbaum Canc Ctr, Dept Med,Gastroenterol Div, Baltimore, MD 21201 USA
6. Baltimore Vet Affairs Hosp, Baltimore, MD 21201 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PO BOX 11806, BIRMINGHAM, AL 35202 USA |
| Subject Category: Oncology |
| IDS Number: 348AG |
| ISSN: 0008-5472 |
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