DNA Nucleotide Excision Repair in Ductal Carcinoma In Situ

Nova Southeastern University, Davie, Florida, USA

Objective. To identify which Ductal Carcinoma In Situ (DCIS) cases will remain indolent versus those will become invasive. Background. DCIS is a non-obligate precursor of invasive breast cancer (BC). 50% of cases progress to invasive BC with no accurate way to identify indolent versus aggressive types. We hypothesized that isolation of invasive cells from 2 pre-existing DCIS cell lines will allow for the identification of biomarkers for invasive and non-invasive DCIS. We further hypothesize that NER is the engine for invasion evolution, leading to DCIS progression to stage I disease. Methods. Using a novel tissue-engineering system, DCIS model systems with isogenically matched contralateral or non-tumor adjacent (NTA) tissues were created. Expression microarray and RNAseq are being used to determine the expression of 20 canonical NER genes. The Unscheduled DNA Synthesis (UDS) assay is being used to determine NER capacity. Results. A comparison of NER capacity of DCIS explants with the isogenically matched contralateral and NTA explants show a reduction in NER capacity in DCIS. NER capacities reflect a continuum of high repair in contralateral falling lower in non-tumor adjacent and the lowest repair in the isogenic DCIS. Supervised analysis reveals that DCISs clustered together with non-disease breast reduction epithelium while DCIS synchronous with stage I BC clustered together with stage I and II BC. Conclusion. This study will differentiate between indolent and aggressive DCIS cases. Ultimately, these data and that of other laboratories will improve DCIS management.