Project description:Colorectal cancer (CRC) is the third most common cancer worldwide and liver metastasis remains the major cause of death in CRC. Extensive genomic analysis provided valuable insight into the pathogenesis and progression of CRC. However, the major proteogenomic characterization of CRC liver metastasis is still unknown. We investigated proteogenomic characterization and performed comprehensive integrative genomic analysis of human colorectal cancer liver metastasis.
Project description:Current clinical therapy of non-small cell lung cancer depends on histo-pathological classification. This approach poorly predicts clinical outcome for individual patients. Proteogenomic characterization analysis holds promise to improve clinical stratification, thus paving the way for individualized therapy. We investigated proteogenomic characterization and performed comprehensive integrative genomic analysis of human large cell lung cancer. Here we analyzed proteomes of 29 paired normal lung tissues and large cell lung cancer, identified significantly deregulated proteins associated with large cell lung cancer.
Project description:To identify DNA accessibility targets regulated by the SWI/SNF subunit SMARCB1 in bladder cancer, we compared the ATAC-seq signals in T24 cells engineered for SMARCB1 knockout, non-targeting control, or SMARCB1 re-expression following knockout. Analysis of altered DNA accessibility profiles revealed new roles for SMARCB1 in the regulation of gene expression in bladder cancer, and suggested new therapeutic opportunities.
Project description:An incomplete view of the (epi)genetic events that drive melanoma initiation and progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. Recent approaches that integrate human melanoma genomic and transcriptomic data provide unprecedented opportunities to discover oncogenic melanoma drivers. One limitation, however, is that human melanoma genome exhibits a radically altered cytogenetic profile. Hence there is a need for biologically-meaningful approaches to identify and validate lesions that drive melanomagenesis. We combined comparative oncogenomic approaches with mouse modeling to identify new cancer genes/pathways that drive melanoma progression. Spontaneously acquired genetic alterations such as copy-number alterations and specific mutations in mouse tumors of defined genetic origin were identified and used to prioritize relevant lesions from the complex human melanoma genomes. This integrated effort confirmed the importance of several genes and pathways previously implicated in melanoma and identified new putative melanoma tumor suppressor genes. Genetic ablation of one such gene, Fes, cooperated with BRafv600E to accelerate melanomagenesis in mice. This comparative oncogenomic approach has therefore helped discover a series of novel melanoma tumor suppressor genes, including FES, with prognostic and therapeutic relevance in human melanoma.
