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In contrast, SAM analysis identified 1,664 transcripts that differed significantly between proliferating and confluent cells, and 1,232 transcripts that differed between fibroblasts derived from AIS-affected individuals and normal male foreskin.
The ARD364 and ARD465 lines express wild-type AR and were derived from individuals who were mosaics for wild-type AR and AR with a premature stop codon [ 7 ] . Hierarchical cluster analysis, based on the expression of 472 of the 487 previously identified transcripts with measurable expression across at least 80% of 24 experiments, separated the fibroblasts into those with gene-expression patterns resembling normal male foreskin fibroblasts and a second group with an expression pattern more similar to labial skin fibroblasts from AIS-affected individuals (Figure 2).
The analysis was based on 2,862 transcripts that differed significantly between proliferating and confluent cells and between fibroblasts derived from AIS-affected individuals and normal male foreskin, respectively, as identified by SAM analysis of the treatment series.
We have previously used a similar approach to delineate the transcriptional programs activated in prostate cancer cells in response to androgen [ 9 ] . We had hoped that comparison of transcriptional responses of normal fibroblasts to those from AIS-affected individuals with varying degrees of genital ambiguity would provide still further insights into androgen's role in genital morphogenesis.
These female AIS-affected individuals are thought to have acquired their AR gene mutations post-zygotically [ 12 ] . ARD364, which showed AR protein expression and binding in the range of normal male foreskin fibroblasts ( [ 7 ] and see Table 1), despite its origin from anatomically female genitalia, had a gene-expression pattern indistinguishable from foreskin fibroblasts of normal males (Figure 2).
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