MspI restriction fragment length polymorphism at the glycoprotein hormone alpha-subunit locus. Association of certain genotypes with neoplasia.
A restriction fragment length polymorphism (RFLP) in the human glycoprotein hormone common alpha-subunit gene has been identified and partially characterized in normal lymphocytes and placentae, established tumor cell lines, and tumor biopsy samples. High molecular weight DNA was digested with the restriction endonuclease MspI, separated by electrophoresis in agarose gels, transferred to nylon membranes by the method of Southern, and hybridized to 32P-labeled human chorionic gonadotropin alpha-subunit cDNA. After autoradiography, bands were detected at 5.3, 3.3, 2.1, 1.6, 0.8 and 0.6 kbp. Presence of the 5.3, 3.3 and 0.6 kbp bands was invariant and uninformative. Patterns missing the 0.8 kbp band and both the 2.1 and 1.6 kbp bands are consistent with separate alleles that occur in placental and lymphocyte DNA with frequencies of 0.44 (15/34) and 0.06 (2/34), respectively. Presence of all three bands (2.1, 1.6 and 0.8 kbp) is indicative of heterozygosity, occurring at a frequency of 0.50 (17/34). Additional restriction patterns, not yet observed in DNA isolated from term placentae or circulating lymphocytes, were detected in DNA obtained from tumor cell lines and fresh tumor tissues at frequencies of 0.79 (15/19) and 0.59 (10/17), respectively. Thus, particular alpha-subunit genotypes are disproportionately represented in tumor-derived DNA, occurring at frequencies 10- to 13-times higher than would be predicted from their occurrence in normal tissue. Paired normal and tumor tissues from the same individual exhibited identical hybridization patterns, suggesting that this RFLP may be representative of a predisposition toward a variety of neoplasias rather than indicative of a change in DNA structure at or near this locus as a result of tumor development.
Cox
G S
GS
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha 68198-3255, USA.
Cosgrove
D E
DE
Haas
M J
MJ
Stiles
W
W
McIntosh
D G
DG
D019003:Deoxyribonuclease HpaII / Q000378:metabolism*; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D014407:Tumor Cells, Cultured
D015292:Glycoprotein Hormones, alpha Subunit; D019003:Deoxyribonuclease HpaII