POSTER ABSTRACTS
#56 Somatic variant landscapes of solid papillary and comedo subtypes of canine mammary tumors from a single dog Sruthi Hundi1,2,3*, Vivi Deckwirth2*, Marjo K Hytönen1,2,3, Antti Sukura3, Hannes Lohi1,2,3* * Authors contributed equally for this work sruthi.hundi@helsinki.fi 1Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland, 2Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland, 3Folkhälsan Research Center, Helsinki, Finland Background /Objectives Breast cancer (BC) is still the most common cancer reported in women and mammary tumor (MT) is also the most common malignancy in intact female dogs. The key goal of this research is to study two rare and less explored subtypes of canine mammary tumor, i) solid papillary subtype and ii) comedo subtype and compare the findings with previous MT discoveries in dogs and humans. Methods An intact female dog diagnosed with simple invasive carcinoma of solid papillary and comedo subtypes was selected, and cell populations from respective tumor sites and normal lobular cells were isolated using the method of laser microdissection. DNA libraries from isolated cells were prepared with PicoPLEX tool kit, followed by whole genome sequencing with about 15X coverage. Data was aligned to the CanFam4 reference, and somatic variants were called, analyzed and compared between subtypes. Results The number of non-silent mutations was 6-fold higher in comedo subtype than in solid papillary subtype. Genes related to MAPK, mTOR and NF-kappaB signaling pathways and adherens junctions were enriched in solid papillary. Genes related to ECM receptor interaction, focal and cell adhesion, PI3K-AKT and cGMP-PKG signaling pathways were enriched in comedo. The affected pathways partially overlap with previous canine and human MT studies. Conclusion The study indicates higher tumor mutation burden in comedo subtype, similar to human findings. The fact that variants were enriched in cell proliferation signaling pathways and junction supports the invasive nature of the tumor, which was identified as HER2 +ve and E Cadherin positivity. Grants Partially supported by Cancer Foundation Finland and Jane and Aatos Erkko Foundation.
99
Made with FlippingBook - Online magazine maker