Phylogenetic modeling of endometriosis gene expression

Endometriosis is the growth of endometrial glands and stroma outside the normal lining of the uterine cavity. Ten to twenty percent of American women develop endometriosis, with forty percent diagnosed infertile. It is an enigmatic disorder, as the etiology and pathophysiology remain unresolved. Our objective was to reveal clonally altered gene expression and identify a genomic biosignature for endometriosis using a phylogenetic analysis of gene‐expression microarray data. Data was polarized and coded into derived and normal states, followed by a maximum parsimony analysis to produce a cladogram representing the genomic classification based on the shared derived characters‐the synapomorphies. Gene linkage was modeled by Genomatix BiblioSphere Pathway Edition software. The analysis identified 1875 clonally altered genes involved in reproductive functions, carcinogenesis, cytoskeleton, apoptosis, immune function, cell proliferation, and the Ras‐Mek‐MAPK pathway. This novel strategy produced a list of clonally shared altered expressions in all the specimens analyzed, and revealed a massive disruption of major regulatory pathways. Interestingly, a number of genes are also involved in gynecologic carcinogenesis. Our analysis exposed genes that may be involved in the malignant transformations within endometriosis cases associated with endometrioid ovarian carcinoma.