Ann‐Marie Patch
A5031578701- Cancer Genomics and Diagnostics
- Pancreatic function and diabetes
- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Ovarian cancer diagnosis and treatment
- Diabetes and associated disorders
- Cutaneous Melanoma Detection and Management
- Fibroblast Growth Factor Research
- Cancer-related gene regulation
- Occupational and environmental lung diseases
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
- Genomics and Phylogenetic Studies
- Endometrial and Cervical Cancer Treatments
- Lung Cancer Treatments and Mutations
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- RNA and protein synthesis mechanisms
- Evolution and Genetic Dynamics
- Cancer Research and Treatments
- Genomics and Rare Diseases
- Protein Degradation and Inhibitors
- Immune Cell Function and Interaction
- Arctic and Antarctic ice dynamics
QIMR Berghofer Medical Research Institute
2016-2025
The University of Queensland
2012-2023
Westmead Institute for Medical Research
2018
Roche (Switzerland)
2018
AstraZeneca (Brazil)
2018
The University of Melbourne
2015
Royal Women's Hospital
2015
University of Exeter
2004-2014
Peninsula College of Medicine and Dentistry
2007-2010
Peninsula Health
2010
Obesity is a serious international health problem that increases the risk of several common diseases. The genetic factors predisposing to obesity are poorly understood. A genome-wide search for type 2 diabetesâsusceptibility genes identified variant in FTO (fat mass and associated) gene predisposes diabetes through an effect on body index (BMI). An additive association with BMI was replicated 13 cohorts 38,759 participants. 16% adults who homozygous allele weighed about 3 kilograms more...
We report 10 heterozygous mutations in the human insulin gene 16 probands with neonatal diabetes. A combination of linkage and a candidate approach family four diabetic members led to identification initial INS mutation. The are inherited an autosomal dominant manner this two other small families whereas 13 patients de novo. Diabetes presented at median age 9 weeks, usually ketoacidosis or marked hyperglycemia, was not associated beta cell autoantibodies, treated from diagnosis insulin....
OBJECTIVE— Insulin gene (INS) mutations have recently been described as a cause of permanent neonatal diabetes (PND). We aimed to determine the prevalence, genetics, and clinical phenotype INS in large cohorts patients with diagnosed infancy, childhood, or adulthood. RESEARCH DESIGN AND METHODS— The was sequenced 285 before 2 years age, 296 probands maturity-onset young (MODY), 463 young-onset type (nonobese, <45 years). None had molecular genetic diagnosis monogenic diabetes....
Context: The interpretation of novel missense variants is a challenge with increasing numbers such being identified and responsibility to report the findings in context all available scientific evidence. Various silico bioinformatic tools have been developed that predict likely pathogenicity variants; however, their utility within diagnostic setting requires further investigation. Aim: aim our study was test predictive value two these tools, sorting intolerant from tolerant (SIFT)...
Transient neonatal diabetes mellitus (TNDM) is diagnosed in the first 6 months of life, with remission infancy or early childhood. For approximately 50% patients, their will relapse later life. The majority cases result from anomalies imprinted region on chromosome 6q24, and 14 patients ATP-sensitive K+ channel (K(ATP) channel) gene mutations have been reported. We determined 6q24 status 97 TNDM. In whom no abnormality was identified, KCNJ11 and/or ABCC8 gene, which encode Kir6.2 SUR1...
Extracellular adenosine is a key immunosuppressive metabolite that restricts activation of cytotoxic lymphocytes and impairs antitumor immune responses. Here, we show engagement A2A receptor (A2AR) acts as checkpoint limits the maturation natural killer (NK) cells. Both global NK-cell-specific conditional deletion A2AR enhanced proportions terminally mature NK cells at homeostasis, following reconstitution, in tumor microenvironment. Notably, A2AR-deficient, retained proliferative capacity...
Abstract As whole-genome sequencing for cancer genome analysis becomes a clinical tool, full understanding of the variables affecting output is required. Here using tumour-normal sample pairs from two different types cancer, chronic lymphocytic leukaemia and medulloblastoma, we conduct benchmarking exercise within context International Cancer Genome Consortium. We compare methods, pipelines validation methods. show that PCR-free methods increasing depth to ∼100 × shows benefits, as long...
Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large exome sequencing date have found recurrent loss-of-function mutations, oncogenic driving events been underrepresented. Here we use a combination whole-genome (WGS) single-nucleotide polymorphism-array profiling show that genomic catastrophes are frequent EAC, with almost third (32%, n=40/123)...
Abstract Knowledge of key drivers and therapeutic targets in mucosal melanoma is limited due to the paucity comprehensive mutation data on this rare tumor type. To better understand genomic landscape melanoma, here we describe whole genome sequencing analysis 67 tumors validation driver gene mutations by exome 45 tumors. Tumors have a low point burden high numbers structural variants, including recurrent rearrangements targeting TERT, CDK4 MDM2 . Significantly mutated genes are NRAS , BRAF...
The importance of epigenetic modifications such as DNA methylation in tumorigenesis is increasingly being appreciated. To define the genome-wide pattern pancreatic ductal adenocarcinomas (PDAC), we captured profiles 167 untreated resected PDACs and compared them to a panel 29 adjacent nontransformed pancreata using high-density arrays. A total 11,634 CpG sites associated with 3,522 genes were significantly differentially methylated (DM) PDAC capable segregating from non-malignant pancreas,...
Abstract To increase understanding of the genomic landscape acral melanoma, a rare form melanoma occurring on palms, soles or nail beds, whole genome sequencing 87 tumors with matching transcriptome for 63 was performed. Here we report that mutational signature analysis reveals subset tumors, mostly subungual, an ultraviolet radiation signature. Significantly mutated genes are BRAF, NRAS , NF1 NOTCH2 PTEN and TYRP1 . Mutations amplification KIT also common. Structural rearrangement copy...
Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting prevent normal folding proinsulin, which leads beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive 15 probands with Functional studies showed resulted diabetes because decreased insulin biosynthesis distinct mechanisms, including deletion, lack translation initiation...
Mutations in EIF2AK3 cause Wolcott-Rallison syndrome (WRS), a rare recessive disorder characterized by early-onset diabetes, skeletal abnormalities, and liver dysfunction. Although early diagnosis is important for clinical management, genetic testing generally performed after the full picture develops. We aimed to identify patients with WRS before any other abnormalities apart from diabetes are present study overall frequency of among permanent neonatal diabetes.The coding regions were...
Understanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge key regulators has predominantly come from mouse studies, rare, naturally occurring mutations establishing their relevance man. This study used a combination homozygosity analysis and Sanger sequencing 37 consanguineous permanent neonatal diabetes search homozygous 29 transcription factor genes...