Hypersensitive Cancer hotspot sequencing panel in patients with two or more subtypes of endometriosis
20 September 2018 (online)
The clinical presentation of endometriosis is highly heterogeneous. In a landmark study we have shown somatic cancer-driver mutations in deep infiltrating endometriosis, with at least one case having multiple sites harboring the same driver mutation. Understanding heterogeneity and differences in lineage of endometriosis may help to understand the diversity of clinical presentation and the varying potential of progression to cancer among its subtypes.
Materials and methods:
We sampled lesions from 27 patients who presented with two or more subtypes of endometriosis, in anatomically distinct locations. DNA extracted from macrodissected tissue was analyzed using a hypersensitive cancer hotspot sequencing panel. Identified mutations were validated with droplet digital PCR. ARID1A and PTEN immunohistochemistry were performed as surrogates for loss of respective proteins due to somatic events.
Preliminary analysis detected mutations in KRAS, NRAS, CTNNB1, EGFR, ERBB2 and PIK3CA in 12 of 24 cases. Loss of PTEN was observed in three cases; none showed loss of ARID1A. Three cases had identical alterations affecting more than one lesion/type of endometriosis. As some lesions were too small for sampling in our panel, validation of detected mutations by droplet digital PCR is pending to confirm potential clonality between sites and endometriosis types.
While malignant transformation of endometriosis appears restricted to the ovaries, new data suggests that some endometriosis may have the capacity to metastasize. Our results suggest clonality between lesions is not uncommon, and site/microenvironment is likely to have a strong influence on the clinical presentation of endometriosis and its malignant potential.