Statistical tests for intra-tumour clonal co-occurrence and exclusivity.

Tumour progression is an evolutionary process in which different clones evolve over time, leading to intra-tumour heterogeneity. Interactions between clones can affect tumour evolution and hence disease progression and treatment outcome. Intra-tumoural pairs of mutations that are overrepresented in a co-occurring or clonally exclusive fashion over a cohort of patient samples may be suggestive of a synergistic effect between the different clones carrying these mutations.

Multi-omics data integration reveals novel drug targets in hepatocellular carcinoma.

Background: Genetic aberrations in hepatocellular carcinoma (HCC) are well known, but the functional consequences of such aberrations remain poorly understood.

Results: Here, we explored the effect of defined genetic changes on the transcriptome, proteome and phosphoproteome in twelve tumors from an mTOR-driven hepatocellular carcinoma mouse model. Using Network-based Integration of multi-omiCS data (NetICS), we detected 74 'mediators' that relay via molecular interactions the effects of genetic and miRNA expression changes.

Spatial Distribution of Private Gene Mutations in Clear Cell Renal Cell Carcinoma.

Intra-tumour heterogeneity is the molecular hallmark of renal cancer, and the molecular tumour composition determines the treatment outcome of renal cancer patients. In renal cancer tumourigenesis, in general, different tumour clones evolve over time. We analysed intra-tumour heterogeneity and subclonal mutation patterns in 178 tumour samples obtained from 89 clear cell renal cell carcinoma patients.

Convergent network effects along the axis of gene expression during prostate cancer progression.

Background: Tumor-specific genomic aberrations are routinely determined by high-throughput genomic measurements. It remains unclear how complex genome alterations affect molecular networks through changing protein levels and consequently biochemical states of tumor tissues.

Results: Here, we investigate the propagation of genomic effects along the axis of gene expression during prostate cancer progression.

Expression and Mutation Patterns of PBRM1, BAP1 and SETD2 Mirror Specific Evolutionary Subtypes in Clear Cell Renal Cell Carcinoma.

Bi-allelic inactivation of the VHL gene on chromosome 3p is the characteristic feature in most clear cell renal cell carcinomas (ccRCC). Frequent gene alterations were also identified in SETD2, BAP1 and PBRM1, all of which are situated on chromosome 3p and encode histone/chromatin regulators. The relationship between gene mutation, loss of protein expression and the correlations with clinicopathological parameters is important for the understanding of renal cancer progression.

A switch in transcription and cell fate governs the onset of an epigenetically-deregulated tumor in .

Tumor initiation is often linked to a loss of cellular identity. Transcriptional programs determining cellular identity are preserved by epigenetically-acting chromatin factors. Although such regulators are among the most frequently mutated genes in cancer, it is not well understood how an abnormal epigenetic condition contributes to tumor onset.