Differential genomic and transcriptomic analysis of invasive lobular and ductal carcinomas.

• DOI: 10.1200/jco.2023.41.16_suppl.579
• Publication Date: 2023-06-04T14:02:11Z
• Authors: Jason A Mouabbi; Funda Meric-Bernstam; Svetlana Khorkova; Polina Turova; Nikita Kotlov; Konstantin Cherny...; Vladimir Kushnarev; Anna Love; Patrick Clayton; Krystle Nomie; Nathan Fowler; Debu Tripathy
• Keywords: CDH1; Invasive lobular carcinoma; Gene signature

579 Background: Invasive lobular carcinoma (ILC) is more aggressive than hormone receptor (HR)-positive invasive ductal (IDC). However, in practice, ILC and IDC are often treated a similar fashion with endocrine therapy chemotherapy. Identifying novel biomarkers, genetic alterations, transcriptomic features, tumor microenvironment (TME) variations could initiate the development of personalized treatment plans for patients ILC. Methods: We collected luminal (non-basal/non-HER2) samples from four datasets (TCGA, METABRIC, RATHER PMC4700448, UQCCR PMC31263747) performed differential expression gene set enrichment analyses, revealing genomic, transcriptomic, TME differences. Using methods Bagaev et al., we quantified activity 29 functional signatures single sample analysis before clustering into five subtypes; statistical significance was measured Mann-Whitney U test. Differential RNA-Seq data completed using DESeq2. Further, analyzed frequency specific biomarkers to identify potential therapeutic options. Mutations biomarker were assessed chi-squared Results: 1,735 (1,442 IDCs 293 ILCs). CDH1 mutations prevalent (56%) compared (6%). Of 44% wild-type CDH1, 90% had low expression. Inference models showed differences transcription factors between IDC. significantly higher TFAP2B, SOCS2, NOSTRIN, THBS4, SCUBE2, GDF9 lower CDCA4, PSMG1, LMOD1, SLC7A5 (adj p < 0.0001 all genes). Analysis that immune enriched high PDL1, CTLA4, LAG3 In comparison, approximately 30% contained enhanced vascularization expressed VEGFA, PDGFRA, PDGFRB. Finally, IDC, tend have statistically significant TROP2 expression, seen basal subtype. Conclusions: distinct genomic TMEs, biomarkers. These can be used as blueprint tailor phenotype-specific interventional clinical trials.