Molecular genetic evidence for different clonal origin of components of human renal angiomyolipomas

Renal angiomyolipoma is a benign neoplasm composed of variable proportions of blood vessels, smooth muscle, and adipose tissue. Smooth muscle, adipose tissue, blood vessels, and adjacent normal kidney tissue were separately m icrodissected from sections prepared from formalin-fixed, paraffin-processe d tissues from angiomyolipomas from 18 women. X chromosome inactivation ana lysis using the methylation pattern at exon 1 of the human androgen recepto r gene on chromosome Xq11-12 was used to study the clonal origin of each co mponent. Nonrandom inactivation of X chromosomes was found in six of the 15 informative tumors. The smooth muscle and adipose tissue showed differing patterns of nonrandom inactivation of X chromosomes in five angiomyolipomas and the same pattern of nonrandom inactivation of X chromosomes in one. Sa mples from the blood vessels showed random inactivation of X chromosomes in all informative cases. Our data showed that the adipose tissue and smooth muscle cells of renal angiomyolipoma are both monoclonal but may arise inde pendently. The coexistence of tumor subclones with morphologic heterogeneit y can lead to the formation of a clinically detectable tumor.