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.


CONCLUSIONS
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.
Walsh
D S
DS
Dermatology Services, Walter Reed Army Medical Center, Washington, DC, USA.
Peacocke
M
M
Harrington
A
A
James
W D
WD
Tsou
H C
HC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology; D019070:Cell Lineage / Q000235:genetics; D002999:Clone Cells / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics; D015203:Reproducibility of Results; D012867:Skin / Q000166:cytology / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D014960:X Chromosome / Q000235:genetics*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D011944:Receptors, Androgen