227 research outputs found
Using BioMart as a framework to manage and query pancreatic cancer data
We describe the Pancreatic Expression Database (PED), the first cancer database originally designed based on the BioMart infrastructure. The PED portal brings together multidimensional pancreatic cancer data from the literature including genomic, proteomic, miRNA and gene expression profiles. Based on the BioMart 0.7 framework, the database is easily integrated with other BioMart-compliant resources, such as Ensembl and Reactome, to give access to a wide range of annotations alongside detailed experimental conditions. This article is intended to give an overview of PED, describe its data content and work through examples of how to successfully mine and integrate pancreatic cancer data sets and other BioMart resources
Field cancerization in breast cancer
Breast cancer affects one in seven women worldwide during their lifetime. Widespread mammographic screening programs and education campaigns allow for early detection of the disease, often during its asymptomatic phase. Current practice in treatment and recurrence monitoring is based primarily on pathological evaluations but can also encompass genomic evaluations, both of which focus on the primary tumor. Although breast cancer is one of the most studied cancers, patients still recur at a rate of up to 15% within the first 10 years post‐surgery. Local recurrence was originally attributed to tumor cells contaminating histologically normal (HN) tissues beyond the surgical margin, but advances in technology have allowed for the identification of distinct aberrations that exist in the peri‐tumoral tissues themselves. One leading theory to explain this phenomenon is the field cancerization theory. Under this hypothesis, tumors arise from a field of molecularly altered cells that create a permissive environment for malignant evolution, which can occur with or without morphological changes. The traditional histopathology paradigm dictates that molecular alterations are reflected in the tissue phenotype. However, the spectrum of inter‐patient variability of normal breast tissue may obfuscate recognition of a cancerized field during routine diagnostics. In this review, we explore the concept of field cancerization focusing on HN peri‐tumoral tissues: we present the pathological and molecular features of field cancerization within these tissues and discuss how the use of peri‐tumoral tissues can affect research. Our observations suggest that pathological and molecular evaluations could be used synergistically to assess risk and guide the therapeutic management of patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland
Longitudinal profiling of circulating tumour DNA for tracking tumour dynamics in pancreatic cancer.
BACKGROUND: The utility of circulating tumour DNA (ctDNA) for longitudinal tumour monitoring in pancreatic ductal adenocarcinoma (PDAC) has not been explored beyond mutations in the KRAS proto-oncogene. Here, we aimed to characterise and track patient-specific somatic ctDNA variants, to assess longitudinal changes in disease burden and explore the landscape of actionable alterations. METHODS: We followed 3 patients with resectable disease and 4 patients with unresectable disease, including 4 patients with ≥ 3 serial follow-up samples, of whom 2 were rare long survivors (> 5 years). We performed whole exome sequencing of tumour gDNA and plasma ctDNA (n = 20) collected over a ~ 2-year period from diagnosis through treatment to death or final follow-up. Plasma from 3 chronic pancreatitis cases was used as a comparison for analysis of ctDNA mutations. RESULTS: We detected > 55% concordance between somatic mutations in tumour tissues and matched serial plasma. Mutations in ctDNA were detected within known PDAC driver genes (KRAS, TP53, SMAD4, CDKN2A), in addition to patient-specific variants within alternative cancer drivers (NRAS, HRAS, MTOR, ERBB2, EGFR, PBRM1), with a trend towards higher overall mutation loads in advanced disease. ctDNA alterations with potential for therapeutic actionability were identified in all 7 patients, including DNA damage response (DDR) variants co-occurring with hypermutation signatures predictive of response to platinum chemotherapy. Longitudinal tracking in 4 patients with follow-up > 2 years demonstrated that ctDNA mutant allele fractions and clonal trends were consistent with CA19-9 measurements and/or clinically reported disease burden. The estimated prevalence of 'stem clones' was highest in an unresectable patient where changes in ctDNA dynamics preceded CA19-9 levels. Longitudinal evolutionary trajectories revealed ongoing subclonal evolution following chemotherapy. CONCLUSION: These results provide proof-of-concept for the use of exome sequencing of serial plasma to characterise patient-specific ctDNA profiles, and demonstrate the sensitivity of ctDNA in monitoring disease burden in PDAC even in unresectable cases without matched tumour genotyping. They reveal the value of tracking clonal evolution in serial ctDNA to monitor treatment response, establishing the potential of applied precision medicine to guide stratified care by identifying and evaluating actionable opportunities for intervention aimed at optimising patient outcomes for an otherwise intractable disease
SEARCHBreast: a new resource to locate and share surplus archival material from breast cancer animal models to help address the 3Rs
Animal models have contributed to our understanding
of breast cancer, with publication of results in
high-impact journals almost invariably requiring extensive
in vivo experimentation. As such, many laboratories hold
large collections of surplus animal material, with only a
fraction being used in publications relating to the original
projects. Despite being developed at considerable cost, this
material is an invisible and hence an underutilised
resource, which often ends up being discarded. Within the
breast cancer research community there is both a need and
desire to make this valuable material available for
researchers. Lack of a coordinated system for visualisation
and localisation of this has prevented progress. To fulfil
this unmet need, we have developed a novel initiative
called Sharing Experimental Animal Resources: Coordinating
Holdings—Breast (SEARCHBreast) which facilitates
sharing of archival tissue between researchers on a
collaborative basis and, de facto will reduce overall usage
of animal models in breast cancer research. A secure
searchable database has been developed where researchers
can find, share, or upload materials related to animal
models of breast cancer, including genetic and transplant
models. SEARCHBreast is a virtual compendium where
the physical material remains with the original laboratory.
A bioanalysis pipeline is being developed for the analysis
of transcriptomics data associated with mouse models,
allowing comparative study with human and cell line data.
Additionally, SEARCHBreast is committed to promoting
the use of humanised breast tissue models as replacement
alternatives to animals. Access to this unique resource is freely available to all academic researchers following
registration at https://searchbreast.org
Introducing SEARCHBreast: a virtual resource to facilitate sharing of surplus animal material developed for breast cancer research
Animals studies have made significant contribution to expanding our knowledge of breast cancer. Often material is leftover and archived. SEARCHBreast provides a platform for collaborative sharing of archived material via a dedicated on-line database whereby users can both share and search available tissue. The SEARCHBreast database has information on over 50 different mouse models, including tissue from PDX models, available to share. With thousands of samples freely available, SEARCHBreast should be the first point of call for any researcher looking for animal material to aid their breast cancer research
SEARCHBreast: A new online resource to make surplus material from in vivo models of breast cancer visible and accessible to researchers
No abstract available
SEARCHBreast: An online resource designed to increase the efficiency of using materials derived from breast cancer studies in animals
No abstract available
The SEARCHBreast portal: A virtual bioresource to facilitate the sharing of surplus animal materials derived from breast cancer studies
The SEARCHBreast portal (https://searchbreast.org/) provides access to a virtual bioresource enabling researchers to access and share material derived from breast cancer related animal studies on a collaborative basis. By registering as members of SEARCHBreast, researchers can browse the SEARCHBreast platform for relevant tissue and models, and request access to these to help answer their specific biological question(s). SEARCHBreast mediates the collaborations formed from requests for these materials. As of July 2016, the virtual bioresource has received 8 requests for tissue and has sent hundreds of tissue samples saving approximately 400 animals. SEARCHBreast is currently developing a bioinformatics pipeline, enabling users to access and mine published data on animal models of breast cancer, potentially helping to reduce experimental redundancy further, prioritising new relevant research
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