A5022355349- Genetic factors in colorectal cancer
- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Multiple and Secondary Primary Cancers
- Geriatric Care and Nursing Homes
- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- HER2/EGFR in Cancer Research
- Digestive system and related health
- Frailty in Older Adults
- Monoclonal and Polyclonal Antibodies Research
- PARP inhibition in cancer therapy
- Radiomics and Machine Learning in Medical Imaging
- Tumors and Oncological Cases
- Cancer, Lipids, and Metabolism
- Lung Cancer Treatments and Mutations
- Pancreatic and Hepatic Oncology Research
- PI3K/AKT/mTOR signaling in cancer
- Computational Drug Discovery Methods
- Glycosylation and Glycoproteins Research
- Gastric Cancer Management and Outcomes
- Melanoma and MAPK Pathways
- Cancer Research and Treatments
- RNA modifications and cancer
- Colorectal Cancer Screening and Detection
University of South Australia
2024-2025
South Australian Health and Medical Research Institute
2020-2025
Flinders University
2020-2024
Ludwig Cancer Research
2008-2023
Flinders Medical Centre
2020
Walter and Eliza Hall Institute of Medical Research
2004-2019
The University of Melbourne
2001-2019
Personalis (United States)
2018
Ludwig Cancer Research
2000-2014
Melbourne Bioinformatics
2014
BindingDB (Author Webpage) is a publicly accessible database currently containing ∼20 000 experimentally determined binding affinities of protein–ligand complexes, for 110 protein targets including isoforms and mutational variants, ∼11 small molecule ligands. The data are extracted from the scientific literature, collection focusing on proteins that drug-targets or candidate which structural present in Protein Data Bank. website supports range query types, searches by chemical structure,...
PURPOSE: Colorectal cancer prognosis is currently predicted from pathologic staging, providing limited discrimination for Dukes stage B and C disease. Additional markers outcome are required to help guide therapy selection individual patients. EXPERIMENTAL DESIGN: A multisite single-platform microarray study was done on 553 colorectal cancers. Gene expression changes were identified between D tumors (three training sets) assessed as a signature in (independent test external validation sets)....
Human colorectal cancer cell lines are used widely to investigate tumor biology, experimental therapy, and biomarkers. However, what extent these established represent maintain the genetic diversity of primary cancers is uncertain. In this study, we profiled 70 for mutations DNA copy number by whole-exome sequencing SNP microarray analyses, respectively. Gene expression was defined using RNA-Seq. Cell line data were compared with those published in The Cancer Genome Atlas. Notably, found...
Activation of the canonical TGF-β signaling pathway provides growth inhibitory signals in normal intestinal epithelium. Colorectal cancers (CRCs) frequently harbor somatic mutations members TGFBR2 and SMAD4, but to what extent SMAD2 or SMAD3 contribute tumorigenesis is unclear. A cohort 744 primary CRCs 36 CRC cell lines were sequenced for SMAD2, analyzed allelic loss by single-nucleotide polymorphism (SNP) microarray analysis. Mutation spectra compared between genes, pathogenicity was...
Abstract Purpose: Mutation of BRAF at the valine 600 residue occurs in approximately 10% colorectal cancers, a group with particularly poor prognosis. The response mutant cancer to recent targeted strategies such as anti-BRAF or combinations MEK and EGFR inhibitors remains limited highly heterogeneous within V600E cohorts. There is clearly an unmet need understanding biology cancers potential subgroups this population. Experimental Design: In biggest yet reported cohort 218 gene expression...
The Support Vector Machine (SVM) is an algorithm that derives a model used for the classification of data into two categories and which has good generalization properties. This study applies SVM to problem virtual screening molecules with desired activity. In contrast typical applications SVM, we emphasize not but enrichment actives by using modified version standard function rank molecules. method employs simple novel criterion picking molecular descriptors uses cross-validation select...
BRAF(V600E) mutations are found in 10% of colorectal cancers (CRCs). The low frequency this mutation therefore makes it a challenging target for drug development, unless subsets patients with higher rates can be defined. Knowledge the concordance between primary-metastasis pairs and impact on outcome would also assist optimal development. We selected primary CRCs from 525 (stages I-IV) evenly matched age (<70 ≥70), gender tumor location (right, left rectum), 81 pairs. BRAF(V600E), KRAS...
Oncogene mutations contribute to colorectal cancer development. We searched for differences in oncogene mutation profiles between metastases from different sites and evaluated these as markers site of relapse.One hundred were screened 19 oncogenes, further 61 87 matched primary cancers analyzed genes with identified mutations. Mutation prevalence was compared (a) liver (n = 65), lung 50), brain 46), (b) cancers, (c) an independent cohort 604). Mutations differing metastasis relapse 859...
Microsatellite instability (MSI) is an established marker of good prognosis in colorectal cancer (CRC). Chromosomal (CIN) strongly negatively associated with MSI and has been shown to be a poor small number studies. However, substantial group "double-negative" (MSI-/CIN-) CRCs exists. The these patients unclear. Furthermore, CIN are each specific molecular changes, such as mutations KRAS BRAF, that have prognosis. It not known which MSI, CIN, the gene primary predictors survival.
Abstract We describe a statistical method for the characterization of genomic aberrations in single nucleotide polymorphism microarray data acquired from cancer genomes. Our approach allows us to model joint effect polyploidy, normal DNA contamination and intra-tumour heterogeneity within unified Bayesian framework. demonstrate efficacy our on numerous datasets including laboratory generated mixtures normal-cancer cell lines real primary tumours.
Most patients with BRAF-mutant metastatic melanoma display remarkable but incomplete and short-lived responses to inhibitors of the BRAF kinase or mitogen-activated protein (MEK), collectively BRAF/MEK inhibitors. We found that inherent resistance these agents in BRAF(V600)-mutant cell lines was associated high abundance c-JUN characteristics a mesenchymal-like phenotype. Early drug adaptation drug-sensitive grown culture as xenografts, patient samples during therapy, consistently...
Background Frameshift mutations in microsatellite instability high (MSI-High) colorectal cancers are a potential source of targetable neo-antigens. Many nonsense transcripts subject to rapid degradation due nonsense-mediated decay (NMD), but with cMS the last exon or near exon-exon junction have intrinsic resistance (NMD). NMD-resistant therefore likely expressed mutant proteins MSI-High tumours. Methods Using antibodies conserved N-termini predicted proteins, we analysed cancer cell lines...
PIK3CA and PTEN mutations are prevalent in colorectal cancer potential markers of response to mitogen-activated protein/extracellular signal-regulated kinase inhibitors anti-EGF receptor antibody therapy. Relationships between phosphoinositide 3-kinase (PI3K) pathway mutation, clinicopathologic characteristics, molecular features, prognosis remain controversial.A total 1,093 stage I-IV cancers were screened for (exons 9 20), KRAS (codons 12-13), BRAF (codon 600) mutations, microsatellite...
Abstract Purpose: About 15% of colorectal cancers harbor microsatellite instability (MSI). MSI-associated gene expression changes have been identified in cancers, but little overlap exists between signatures hindering an assessment overall consistency. Little is known about the causes and downstream effects differential expression. Experimental Design: DNA microarray data on 89 MSI 140 microsatellite-stable (MSS) from this study 58 77 MSS cases three published reports were randomly divided...
Studies employing mouse models have identified crypt base and position +4 cells as strong candidates for intestinal epithelial stem cells. Equivalent cell populations are thought to exist in the human intestine; however robust specific protein markers lacking. Here, we show that small large intestine, PHLDA1 is expressed discrete some In adenomas, was a subset of undifferentiated predominantly Ki-67-negative neoplastic cells, suggesting basic hierarchy differentiation retained early...
Partial suppression of the inflammatory gp130-Jak-Stat pathway inhibits intestinal tumor growth.
Objective Tumour-infiltrating lymphocyte (TIL) response and deficient DNA mismatch repair (dMMR) are determinants of prognosis in colorectal cancer. Although highly correlated, evidence suggests that these independent predictors outcome. However, the prognostic significance combined TIL/MMR classification how this compares to major genomic transcriptomic subtypes remain unclear. Design A prospective cohort 1265 patients with stage II/III cancer was examined for status BRAF / KRAS mutations....
ADP-ribosylation is an important posttranslational protein modification that regulates diverse biological processes, controlled by dedicated transferases and hydrolases. Here, we show frequent deletions (∼30%) of the