VON HIPPEL-LINDAU DISEASE GENE DELETION DETECTED IN MICRODISSECTED SPORADIC HUMAN COLON-CARCINOMA SPECIMENS

The progression of human malignancies is thought to involve the inacti vation or loss of tumor suppressor genes. Previous studies have sugges ted that inactivation of tumor suppressor genes on chromosomes 5q, 17p , 18q, and 8p play a role in the development of colorectal carcinoma. However, chromosome 3p at the von Hippel-Lindan disease (VHL) gene loc us (3p25-26) has not been previously implicated in the development or progression of sporadic colorectal carcinoma. The authors have analyze d VHL gene alterations on chromosome 3p in sporadic human colon carcin omas and adenomas using modified microdissection techniques. These tec hniques allow for procurement and analysis of selected subpopulations of cells from both paraffin-embedded and frozen human tumor specimens. MIL disease gene deletion was detected by polymerase chain reaction ( PCR) and single-strand conformation polymorphism (SSCP) analysis in mi crodissected colon carcinoma specimens. Allelic loss of VHL gene was d etected in 7 of 11 (64%) informative patients who underwent colectomy for primary sporadic colon carcinoma. However, no allelic loss of VHL gene was shown in colonic adenomas of eight informative patients. Thes e results indicate that VHL disease gene deletion frequently occurs in sporadic colon carcinoma. Because this deletion was not present in ad enomas, VHL gene may play a role in colonic carcinogenesis and represe nt a relatively late event in colonic neoplasia progression. Additiona lly, microdissection of tissue sections may be especially useful in de tecting allelic loss in PCR-based studies of infiltrating tumors, part icularly when the tumor cells represent a relatively small percentage of the total cell population. This is a US government work. There are no restrictions on its use.