A5022229450- Genetic factors in colorectal cancer
- Colorectal Cancer Treatments and Studies
- Colorectal Cancer Screening and Detection
- Epigenetics and DNA Methylation
- Gastric Cancer Management and Outcomes
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
- RNA modifications and cancer
- Wnt/β-catenin signaling in development and cancer
- TGF-β signaling in diseases
- PI3K/AKT/mTOR signaling in cancer
- Pancreatic and Hepatic Oncology Research
- Colorectal Cancer Surgical Treatments
- Metastasis and carcinoma case studies
- Helicobacter pylori-related gastroenterology studies
- Melanoma and MAPK Pathways
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Inflammatory mediators and NSAID effects
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Digestive system and related health
- Cancer, Lipids, and Metabolism
- Angiogenesis and VEGF in Cancer
- Clinical practice guidelines implementation
QIMR Berghofer Medical Research Institute
2014-2023
The University of Queensland
2012-2023
Royal Brisbane and Women's Hospital
2014
Royal Brisbane and Women's Hospital Foundation
2008-2011
Hospital Research Foundation
2008-2011
In-Q-Tel
2011
// Catherine E. Bond 1 , Diane M. McKeone Murugan Kalimutho 2 Mark L. Bettington 1, 3, 4 Sally-Ann Pearson Troy D. Dumenil Leesa F. Wockner 5 Matthew Burge 6 Barbara A. Leggett 4, 7 Vicki L.J. Whitehall 8 Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia Signal Transduction 3 Envoi Specialist Pathologists, School of Medicine, University Cancer and Population Studies, Department Oncology, Royal Brisbane Women's Hospital,...
Abstract Bone morphogenic proteins (BMPs) are members of the TGFB growth factor superfamily with well‐described functions in bone formation. Although disrupted BMP signalling tumor development has more recently been investigated, a role for BMP3 colorectal cancer (CRC) remained largely unexplored. The aim this study was to investigate disruption CRCs relation both traditional and serrated pathways progression. down‐regulated as assessed by real‐time PCR 50 56 primary tumors (89%). Bisulfite...
Abstract Oncogenic PIK3CA mutations contribute to colorectal tumorigenesis by activating AKT signaling decrease apoptosis and increase tumor invasion. A synergistic association of mutation with KRAS has been suggested resistance antiepidermal growth factor receptor inhibitor therapy for advanced cancer, although studies have conflicting. We sought clarify this examining frequency in relation other key molecular features defined pathways tumorigenesis. was assessed high resolution melt...
Colorectal cancer is a major cause of death and approximately 20% arises within serrated polyps, which are under-recognized poorly understood. Human colorectal polyps frequently exhibit both oncogenic BRAF mutation widespread DNA methylation changes, important in silencing genes restraining neoplastic progression. Here, we investigated whether vivo induction mutant Braf sufficient to result coordinated promoter changes for multiple cancer-related genes. The BrafV637E was induced murine...
Background & AimsColorectal cancer is an epigenetically heterogeneous disease, however, the extent and spectrum of CpG island methylator phenotype (CIMP) not clear.MethodsGenome-scale methylation transcript expression were measured by DNA Methylation RNA microarray in 216 unselected colorectal cancers, findings validated using The Cancer Genome Atlas 450K sequencing data. Mutations epigenetic regulators assessed CIMP-subtyped exomes.ResultsCIMP-high cancers dichotomized into CIMP-H1 CIMP-H2...
WNT activation is a hallmark of colorectal cancer. BRAF mutation present in 15% cancers, and the role mutations signaling regulators this context unclear. Here, we evaluate mutational landscape mutant cancers.we performed exome-sequencing on 24 cancers analyzed these data combination with 175 publicly available cancer exomes. We assessed somatic regulators, hotspot driver analyses to identify potential drivers signaling. The effects Apc Braf were modelled, vivo, using Apcmin/+...
Abstract The majority of “serrated pathway” colorectal cancers have mutation the BRAF oncogene and display CpG island methylator phenotype (CIMP). Half these microsatellite instability (MSI) an excellent prognosis. In absence MSI (microsatellite stable, MSS), has been associated with a particularly poor “Traditional are wild type. Mutation p53 is common this correlates advanced stage. We therefore hypothesized that would be in MSS/ mutant cancer. One thousand eighty‐one were screened for to...
The BRAF oncogene is mutated in 15% of sporadic colorectal cancers. Approximately half these mutant cancers demonstrate frequent frameshift mutations termed microsatellite instability (MSI), but are diploid and chromosomally stable. wild type typically stable (MSS) instead acquire chromosomal (CIN). In cancers, CIN associated with a poor outcome. that MSS, present at an advanced stage have particularly prognosis. We previously demonstrated clinical molecular similarities between MSS or...
Sessile serrated adenomas with BRAF mutation progress rapidly to cancer following the development of dysplasia (SSAD). Approximately 75% SSADs methylate mismatch repair gene MLH1, develop deficiency and resultant cancers have a good prognosis. The remaining mutant traditional (TSA) into microsatellite stable poor reason for this dichotomy is unknown. In study, we assessed genotypic frequency MLH1–93 polymorphism rs1800734 in TSAs determine if uncommon variant A allele predisposes MLH1...
The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause unknown. CIMP associated with microsatellite instability but also found in BRAF mutant stable cancers that are poor prognosis. isocitrate dehydrogenase 1 (IDH1) gene causes glioma due activating mutation produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cancer. mutational hotspot was screened 86 CIMP-positive and 80...
PRDM5 is an epigenetic regulator that has been recognized as important tumour suppressor gene. Silencing of by promoter hypermethylation demonstrated in several cancer types and loss results upregulation the Wnt pathway increased cellular proliferation. not extensively investigated specific subtypes colorectal cancers. We hypothesized it would be more commonly methylated inactivated serrated cancers are hallmarked a BRAF V600E mutation methylator phenotype, compared to traditional wild...
The BRAF (V600E) mutation in colorectal cancers that are microsatellite stable (MSS) confers a poor patient prognosis, whereas mutant microsatellite-unstable (MSI) have an excellent prognosis. wild type typically MSS and display chromosomal instability (CIN). CIN has not been extensively studied on genome-wide basis relation to mutational status cancer. mutant/MSS (BRAFmut/MSS) (n = 33) mutant/MSI (BRAFmut/MSI) 30) were compared for presence of copy number aberrations (CNAs) indicative CIN,...
The serrated neoplasia pathway gives rise to a distinct subgroup of colorectal cancers distinguished by the presence mutant BRAFV600E and CpG Island Methylator Phenotype (CIMP). BRAF CRC are commonly associated with microsatellite instability, which have an excellent clinical outcome. However, proportion retain stability dismal prognosis. molecular drivers responsible for development this cancer unknown. To address this, we established murine model stable comprehensively investigated exome...
// Futoshi Kawamata 1, 2, * , Ann-Marie Patch 3, Katia Nones 3 Catherine Bond 1 Diane McKeone Sally-Ann Pearson Shigenori Homma 2 Cheng Liu 5 Lochlan Fennell Troy Dumenil Gunter Hartel 4 Nozomi Kobayasi Hideki Yokoo Moto Fukai Hiroshi Nishihara Toshiya Kamiyama Matthew E. Burge 6 Christos S. Karapetis 7 Akinobu Taketomi Barbara Leggett 5, Nicola Waddell # and Vicki Whitehall 8, Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia Hokkaido...
Sessile serrated lesions (SSLs) are common across the age spectrum, but BRAF mutant cancers arising occur predominantly in elderly. Aberrant DNA methylation is uncommon SSL from young patients. Here, we interrogate role of ageing and initiation progression.We used an inducible model Braf mutation to direct recombination oncogenic V637E allele murine intestine. was activated after periods ageing, tissue assessed for histological, gene expression changes thereafter. We also investigated...
Researching the murine epigenome in disease models has been hampered by lack of appropriate and cost-effective DNA methylation arrays. Here we perform a comprehensive, comparative analysis between Mouse Methylation BeadChip (MMB) reduced-representation bisulfite sequencing (RRBS) two colorectal carcinogenesis. We evaluate coverage, variability, ability to identify differential RRBS MMB. show that MMB is an effective tool for profiling methylome performs comparably with RRBS, identifying...
Abstract Background & Aims WNT activation is a hallmark of colorectal cancer. BRAF mutation present in 15% cancers, and the role mutations signaling regulators this context unclear. Here we evaluate mutational landscape mutant cancers. Methods We performed exome-sequencing on 24 cancers analysed these data combination with 175 publicly available cancer exomes. assessed somatic regulators, hotspot driver analyses to identify potential drivers signaling. The effects Apc Braf were modelled,...
Abstract BACKGROUND: Colorectal cancer is an epigenetically heterogeneous disease, however the extent and spectrum of CpG Island Methylator Phenotype (CIMP) not clear. RESULTS An unselected cohort 216 colorectal cancers clustered into five clinically molecularly distinct subgroups using Illumina 450K DNA methylation arrays. CIMP-High were most frequent in proximal colons female patients. These dichotomised CIMP-Hl CIMP-H2 based on profile which was supported by over representation BRAF (74%,...