Aim: To investigate and identify biological mechanisms behind endometriosis-associated ovarian cancer (EAOC). To develop clinical analyzes for the identification of premalignant lesions and early signs of EAOC.
Background: Endometriosis is an often-neglected benign disease that affects 10–18% of young fertile women. Endometriosis can turn into ovarian cancer (OC) later in life but often gives rise to significantly reduced quality of life, chronic abdominal pain and infertility much earlier. OC is the gynecological cancer that has the highest mortality due to unclear symptoms and diagnosis in late stages. There are no known predictive molecular markers or signs indicating which women with endometriosis are at risk of developing OC.
Hypothesis: With modern NGS, we can identify somatic mutations in surgically removed endometriosis, consistent with increased risk of OC later in life. Somatic mutations compatible with increased risk of EAOC can be measured with ultra-sensitive mutation assays in cervical fluid biopsies. Components in the SWI/SNF complex are involved in the development of EAOC.
Method: Exome sequencing of EAOC paired with endometriosis surgically removed earlier in life. Verification and validation with ddPCR, SiMSen-Seq for specific somatic mutations and immunohistochemistry. Gene assay construction. Functional studies with inactivation of identified mutations in the Swi/Snf complex.
Preliminary data: Several known hot-spot mutations have been identified by our exomseq. Of particular interest are mutations in ARID1a, part of the Swi / snf complex.
Significance: Identification of biological markers to develop EAOC allows us to provide the young woman with endometriosis active surveillance and later prophylactic surgery in order to reduce the risk of OC and save lives.