Patterns of X chromosome inactivation in sporadic basal cell carcinomas: Evidence for clonality

Background: Some basal cell carcinomas (BCCs) contain genetic mutations, suggesting that the lesion is composed of a monoclonal population of cells. Clonality, a distinguishing feature of neoplasia, can be inferred by referencing clonal markers such as the pattern of X chromosome inactivation. The X-linked human androgen receptor gene (HUMARA; GenBank) contains a polymorphic DNA marker that reliably illustrates the pattern of X chromosome inactivation in a tissue. Objective: Our purpose was to determine the clonality of sporadic BCCs by examining patterns of X chromosome inactivation. Methods: The patterns of X chromosome inactivation in paired samples of normal skin and sporadic BCCs from 24 women were compared by means of the HUMARA gene assay. Results: All samples from normal skin displayed random X chromosome inactivation, consistent with lyonization. In 15 of 25 tumor samples (60%), nonrandom X chromosome inactivation was detected, consistent with monoclonality. Conclusion: At least some sporadic BCCs are composed of a monoclonal population of cells, strengthening the contention that a collection of mutations confers a growth advantage to this epithelial lesion. (J Am Acad Dermatol 1998;38:49-55.)