MALIGNANT TRANSFORMATION OF NONTROPHOBLASTIC CELLS IS ASSOCIATED WITHTHE EXPRESSION OF CHORIONIC-GONADOTROPIN BETA-GENES NORMALLY TRANSCRIBED IN TROPHOBLASTIC CELLS

The beta subunit of human chorionic gonadotropin (hCG beta) is encoded by four nonallelic CG beta genes. An assay was developed for distingu ishing type I CG beta allelic genes beta 7 and beta 6, which possess a GCC codon corresponding to an alanine at position 117 of hCG beta, fr om type II CG beta genes beta 8, beta 5, and beta 3 and its allele bet a 9, which possess a GAC codon corresponding to an aspartic acid at th e same position. In normal trophoblast, hCG beta is encoded by type II CG beta genes, whereas normal nontrophoblastic tissues of differing h istological origin (breast, prostate, skeletal muscle, bladder, adrena l glands, thyroid, colon, and uterus) express only type I CG beta gene s. We studied the expression of CG beta genes in 86 tumor specimens co llected from patients with breast, bladder, prostate, and thyroid canc er and found that up to 61% of these nontrophoblastic tumors expressed type II CG beta genes. Experiments performed on tumor tissues and the ir normal counterparts confirmed that the malignant transformation of nontrophoblastic cells is associated with the expression of type II CG beta genes, These findings provide the basis for a simple test (the C G117 assay) that may be useful for the diagnosis of the most frequent malignancies.