Project description:We propose to definitively characterise the somatic genetics of triple negative breast cancer through generation of comprehensive catalogues of somatic mutations in breast cancer cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.
Project description:To investigate whether the mechanism of whole-genome doubling (WGD) results in distinct genomic and transcriptomic phenotypes, we compared three routes to WGD against their respective parental aneuploid controls across two triple-negative breast cancer (TNBC) cell lines (HCC1806 and MDA-MB-231). WGD mechanisms included naturally occurring cell-cell fusion and two drug-induced cell-cycle error mechanisms: mitotic slippage (MS) and cytokinesis failure (CF). All populations were profiled in biological triplicate by TagSeq (3' tag-based RNA-seq) for transcriptomic analysis and low-pass whole-genome sequencing (WGS) for copy-number profiling.
Project description:Twenty-four triple-negative breast cancer and 14 adjacent normal tissues were collected from breast cancer patients during surgeries at National Taiwan University Hospital (NTUH, Taipei, Taiwan). All triple-negative breast cancer samples were invasive ductal carcinomas (IDC) and were negative in immunohistochemical statuses of ER, PR, and HER2 receptors, as confirmed by professional pathologists. Treatment procedure of all patients followed the National Comprehensive Cancer Network (NCCN) guideline. All samples were neoadjuvant-free and were collected before systemic chemotherapy treatments. Written informed consent was obtained from all patients who participated in this study. Using human tissues for research in this study was approved by the institutional review board at NTUH. A novel set of 25-miRNA signature identified in this study was able to effectively distinguish between triple-negative breast cancer and adjacent normal tissues. Moreover, we documented the first evidence of seven polycistronic miRNA clusters preferentially harboring deregulated miRNA genes in triple-negative breast cancer.
Project description:10 biopsies before treatment from triple negative patients with complete response were collected. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Affymetrix HuGene1.1ST. The biopsies were classified into Good (major or complete) or Poor (absent or minor) therapeutic response subgroup. Whole genome expression of triple negative breast cancer tissues were measured before neoadjuvant chemotherapy