BACKGROUND. Adenoid cystic carcinoma (ACC) is a rare malignancy arising in salivary glands and other sites, characterized by high rates of relapse and distant spread. Recurrent/metastatic (R/M) ACCs are generally incurable, due to a lack of active systemic therapies. To improve outcomes, deeper understanding of genetic alterations and vulnerabilities in R/M tumors is needed. METHODS. An integrated genomic analysis of 1,045 ACCs (177 primary, 868 R/M) was performed to identify alterations associated with advanced and metastatic tumors. Intratumoral genetic heterogeneity, germline mutations, and therapeutic actionability were assessed.
Restoration initiatives of ecosystems transformed by human actions require optimisation of eradication measures of introduced species, particularly in fragile insular ecosystems. We studied aspects of the spatial ecology of introduced feral cats (Felis catus) on subantarctic Auckland Island of New Zealand to assist eradication efforts of pests from this remote, biologically rich island. Firstly, we estimated home range sizes and identified core areas of activity based on movement-rooted dynamic Brownian bridge models. Second, we used resource selection functions with generalised linear mixed models to identify seasonal patterns of space use associated to topographic, vegetation and other landscape predictors. Lastly, we quantified cats daily movement rates within home ranges. Average home range size was larger than on other offshore islands and mainland New Zealand, which might relate to lower cat densities and the abundance and predictability of food resources on the island. Cats mostly selected mosaic areas of forest, shrubs and tall tussocks near the coast, and in predominantly flat areas or nearby steep cliffs, which are all typical habitats of seabirds and terrestrial birds. Cats also selected alpine short tussocks during the cold season, likely related to the upsurge of mice (Mus musculus) due to tussock mast seeding and to transiting to steep cliffy areas. Male cats had home ranges that were larger, contained more core areas, and covered longer daily distances in the warm season than females, which might be associated with different breeding and reproductive behaviour. Eradication tools will need to target all habitats on Auckland Island with increased efforts in areas of identified higher use by cats. Understanding aspects of pest species' spatial ecology on offshore islands worldwide can assist decision-makers in optimising eradication programs such as Predator Free 2050 in New Zealand.
Superimposing responsive digital effects onto sand in a sandbox places educators, students, and policy makers in an augmented reality, offering a hands-on way to explore geoscience processes.
3622 Background: While many sequencing assays may be geared for short variants (SV), more complex biomarkers such as genomic loss of heterozygosity (gLOH) score, also referred to as homologous recombination deficiency (HRD) score, require higher tumor purity for confident detection. Practical methods to increase tumor nuclei percentage (TN%) from pathology specimens are needed to achieve biomarker results to maximize patient matching to approved therapies and/or clinical trial enrollment. Methods: Tumor purity of specimens was determined by the computational analysis pipeline component of the FDA-approved NGS assay, FoundationOneCDx. In the validation study, specimen purities for each tissue block were compared following either no enrichment (UnE, n=46), pathologist-directed enrichment by straight razor blade (RBE, n=30) or precision needle punch (NPE, n=47). Post-enrichment H&E slides confirmed target region sampled for the NPE arm. Based upon validation data, the needle punch process was implemented for the Lung-MAP prospective clinical trial (LM-NPE). TN% was compared between the first 55 tested LM-NPE specimens and the validation study to assess performance on real-world samples outside of a controlled validation experiment. Results: The mean computational TN% in the 4 groups were: UnE: 33%; RBE: 30%; NPE: 52%; and LM-NPE: 48%. In the validation study, NPE had significantly higher purity than both UnE and RBE (p<0.001); in the trial arm, LM-NPE performed equivalently to NPE (p=0.344). Based upon a 30% tumor purity cutoff, gLOH could be determined for 52% UnE, 50% RBE, 89% NPE and 71% LM-NPE. Comparing NPE and LM-NPE groups reveals no statistical difference in Pass/Fail rates for gLOH determination (p=0.883; Fisher’s Test). Conclusions: Precision needle punch cores from tissue blocks have elevated tumor purity, and consequently, a greater number of successful gLOH determinations. Moreover, this process is rapid and inexpensive. Precision punches may constitute best practice with respect to enriching tumor cells from low-purity specimens for biomarker detection in a routine laboratory specimen-processing setting. [Table: see text]
6557 Background: Clinico-genomic data sharing is consistently identified by the global oncology community as a critical requirement to accelerate the discovery and development of new targeted therapies. However, lack of effective collaborative models, fragmented and lengthy legal contracting processes, paucity of funding, and inadequate technological platforms have historically been obstacles for effective data sharing. Methods: In 2015, 10 US academic medical centers (AMC) and Foundation Medicine Inc. (FMI) formed PMEC. Feasibility assessments included creation of a master agreement across sites and willingness to use a central IRB. Oversight and research steering committees were created within the consortium. Through a centralized, secure web-based platform, FoundationInsight, we combined and shared de-identified, harmonized comprehensive FoundationOne genomic profiling data. Research proposals mining this data warehouse are invited quarterly from participant AMCs and peer-reviewed; approved studies are executed at all sites. Results: All 10 AMCs collaborated to execute a master registry participation agreement, followed by a master IRB protocol (New England IRB # 120180008), subsequently approved by individual site IRBs. Since its launch, the PMEC database has grown, on average, 60% per year, to now house over 14,000 cases. The shared dataset covers all tumor types (most commonly lung [17.2%], gastrointestinal [13.8%] and breast [9.2%]), encompasses genomic alterations in >300 genes, and reports relevant supplementary data such as tumor mutation burden and microsatellite instability status. To date, 15 studies have been proposed and evaluated using this platform, with 2 projects currently approved and in progress. Conclusions: We demonstrated the feasibility of creating a collaborative academic consortium that facilitates data sharing and potential discovery efforts in oncology. Technology solutions can accelerate the ability of AMCs, in partnership with central labs, to share and harmonize data to advance precision medicine. This approach lays the groundwork for conducting prospective, biomarker-enriched clinical trials among participating AMCs.
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