The Continuous Transcriptomic Profiling of Drosophila Ras-related Tumors Reveals the Critical Roles of Notch and Toll Signaling Pathway in Driving Tumor Malignancies

By conducting EMS screening within oncogenic Ras benign tumors (RasV12), we identified ten malignant tumor models (RasV12; X-/-) within the drosophila melanogaster eye-antennal disc organ. To mimic longitudinal surveillance of tumor progression, we selected malignant tumors (RasV12; X-/-) at 5, 9, and 13 days, along with control groups (WT and RasV12) at 5 days, for phenotypic quantification and transcriptome profiling. Integrating phenotypic data with transcriptome profiling, we elucidated the gene regulatory programs responsible for distinct phenotypes, including larval tumor burden, tumor volume, neighboring tissue invasion, and tumor-mediated cachexia. Furthermore, we analyzed the chromatin accessibility of specific malignant tumors (RasV12; fry-/-) during tumor progression to delineate the dynamic changes in transcription factor regulation of target genes supporting tumor overgrowth. Consequently, our efforts generated a large multi-omics dataset (bulk RNA-seq and bulk ATAC-seq) of malignant tumors at different stages, providing valuable insights into the molecular mechanisms underlying benign-to-malignant tumor transformation.