A high prevalence of mpox in men who have sex with men and in people with HIV, plus visually striking and contagious lesions, have raised concerns for mpox stigma. 24 PCR-confirmed mpox patients were surveyed over the course of three months, utilizing an mpox stigma scale adapted from the HIV Stigma Scale plus assessment of pain, analgesic efficacy, and healthcare experiences. Participants were cis-male (100%), with male sexual partners (96%), mostly African-American (88%), and living with HIV (79%). Patients answered 4-16 of 24 (mean 10) stigma questions affirmatively, particularly related to negative effects of mpox on the LGBTQ community. 79% reported pain, most commonly of limbs and perianal area, with perianal pain being rated most severe. The most effective pain relief occurred with opioids (100% major relief, n = 2) and tecovirimat (63% major relief, 25% moderate, n = 16). Patients were satisfied with care provided at the studied clinics, but had negative experiences at all other mentioned sites.

Precision oncology relies on advanced sequencing technologies to guide treatment strategies, yet effectively translating genomic data into actionable insights remains a critical challenge. The Personalized OncoGenomics (POG) program at BC Cancer utilizes whole genome and transcriptome analysis (WGTA), providing a comprehensive view of the molecular biology of advanced cancer patient tumours, with over 1200 patients enrolled to-date. This analysis relies on curated clinical knowledgebases linking cancer variants and their clinical relevance, but the breadth and utility of these can be limited by access restrictions or missing information. CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is an open-access, expert moderated, crowd-sourced knowledgebase of clinically relevant cancer variants that aims to address these limitations and is one of several sources used for variant interpretation in POG. Based on a retrospective cohort of POG cases, we evaluated the knowledgebase coverage of genes and variants involved in treatment recommendations from the molecular tumour board (MTB) as well as those suggested by genome analysts. We also considered the impact of quality of evidence on MTB recommendations and patient treatments. We found more than 95% of patients had an alteration considered clinically actionable by the MTB, demonstrating the benefit of WGTA paired with open-source automated variant matching and reporting software. Clinical interpretations derived from CIViC represented nearly 50% of therapeutic evidence reported at the MTB, emphasizing the role of open-access knowledge in precision oncology. Additionally, we identified genome signatures as a critical area with clinical implications requiring further curation efforts and evidence model development.

SUMMARYSpruces (Picea spp.) are coniferous trees widespread in boreal and mountainous forests of the northern hemisphere, with large economic significance and enormous contributions to global carbon sequestration. Spruces harbor very large genomes with high repetitiveness, hampering their comparative analysis. Here, we present and compare the genomes of four different North American spruces: the genome assemblies for Engelmann spruce (Picea engelmannii) and Sitka spruce (Picea sitchensis) together with improved and more contiguous genome assemblies for white spruce (Picea glauca) and for a naturally occurring introgress of these three species known as interior spruce (P. engelmannii × glauca × sitchensis). The genomes were structurally similar, and a large part of scaffolds could be anchored to a genetic map. The composition of the interior spruce genome indicated asymmetric contributions from the three ancestral genomes. Phylogenetic analysis of the nuclear and organelle genomes revealed a topology indicative of ancient reticulation. Different patterns of expansion of gene families among genomes were observed and related with presumed diversifying ecological adaptations. We identified rapidly evolving genes that harbored high rates of non‐synonymous polymorphisms relative to synonymous ones, indicative of positive selection and its hitchhiking effects. These gene sets were mostly distinct between the genomes of ecologically contrasted species, and signatures of convergent balancing selection were detected. Stress and stimulus response was identified as the most frequent function assigned to expanding gene families and rapidly evolving genes. These two aspects of genomic evolution were complementary in their contribution to divergent evolution of presumed adaptive nature. These more contiguous spruce giga‐genome sequences should strengthen our understanding of conifer genome structure and evolution, as their comparison offers clues into the genetic basis of adaptation and ecology of conifers at the genomic level. They will also provide tools to better monitor natural genetic diversity and improve the management of conifer forests. The genomes of four closely related North American spruces indicate that their high similarity at the morphological level is paralleled by the high conservation of their physical genome structure. Yet, the evidence of divergent evolution is apparent in their rapidly evolving genomes, supported by differential expansion of key gene families and large sets of genes under positive selection, largely in relation to stimulus and environmental stress response.

Background: Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing and analysis (WGTA) present an opportunity to align a much larger proportion of patients to therapies. Patients and methods: Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected. Results: Clinically actionable targets were identified for 83% of patients, of which 37% of patients received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, poly-ADP ribose polymerase inhibitors and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%) and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies. Conclusions: Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care.

Dramatic and durable responses to immune checkpoint inhibitors (ICIs) have been observed across multiple tumor types, but identifying the patients most likely to respond to these drugs remains challenging, particularly in the context of metastatic and pre-treated disease. Recent clinically approved biomarkers for patient selection are tumor agnostic, but currently all approved markers are evaluated independently. Through the Personalized Onco Genomics (POG) program at BC Cancer, we aimed to study the impact of evaluating multiple biomarkers in a tumor agnostic cohort. We performed whole genome and transcriptome analysis (WGTA) on fresh tumor biopsies from a heterogeneous pan-cancer cohort of 82 patients with advanced metastatic disease subsequently treated with ICIs. Established biomarkers, including tumor mutation burden (TMB) and CD8+ T cell scores, were able to distinguish responders in our advanced and pre-treated cohort. Additionally, we discovered that combining multiple biomarkers provided the best stratification of patients, suggesting a multifaceted approach, such as WGTA, may be suitable for more accurate identification of patients that may benefit from ICIs. As such, we have initiated a Phase II clinical trial, CAPTIV-8 (NCT04273061), which is distinctive in its use of WGTA to evaluate multiple markers including TMB, CD8+ T cell scores, an M1-M2 macrophage score and viral integration to select patients most likely to respond to atezolizumab. Clinical and genomic data prospectively collected from two hundred patients will be evaluated to test the efficacy of combining these biomarkers and identify additional biomarkers of response which can be used to guide treatment with ICIs. Citation Format: Emma Titmuss, Alexandra Pender, Erin Pleasance, Scott Brown, Cameron J. Grisdale, James Topham, Yaoqing Shen, Melika Bonakdar, Gregory A. Taylor, Laura Williamson, Karen Mungall, Eric Chuah, Andrew J. Mungall, Richard A. Moore, Jean-Michel Lavoie, Stephen Yip, Howard Lim, Daniel J. Renouf, Sophie Sun, Steven J. Jones, Robert Holt, Marco A. Marra, Janessa Laskin. CAPTIV-8: A prospective trial of atezolizumab using a multivariate model incorporating whole genome and transcriptome analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1647.

Abstract Sequencing technology is increasingly essential in clinical cancer management. The majority of clinical cancer sequencing has focused on panel approaches, but recent trials have begun to report the use of transcriptome expression profiling to match patients to therapy. The Personalized OncoGenomics (POG) program at BC Cancer has sequenced over 500 patient tumors, integrating both whole genome and transcriptome data to inform treatment options for patients with advanced or metastatic disease. Here we present 570 patients who were sequenced from 2012 to 2017 and reviewed at the POG multidisciplinary molecular tumor board. Genome and transcriptome information identified clinically actionable targets in 83% (475/570) of sequenced cases, with 37% (209/570) receiving POG-informed therapy. Overall, 248 whole genome and transcriptome sequencing analysis (WGTA)-informed treatments were administered, with some patients receiving multiple treatment courses. Of the treated cases, 46% (114/248) were reported to have physician-assessed clinical benefit. Clinical benefit was assessed as per standard of care rather than strict timing as per RECIST criteria. Mutation, copy number, structural variant, expression, and genome signature data were all used individually or in combination to inform treatments. Treatments based in whole or in part from RNA expression data were the largest subgroup (66.9%, 166/248), and patients in this group had similar proportion of clinical benefit compared to those receiving treatments informed by DNA-based data. Importantly, the use of RNA data resulted in 14.5% (36/248) additional patients receiving WGTA-informed treatments with clinical benefit. Patients were directed to clinical trials, treated with therapeutics in off-label indications, or positioned to genomically-informed standard of care options. For a subset of 42 cases where the planned next line of therapy was documented prior to WGTA analysis, 76.2% (32/42) of genomically-informed standard therapies were different from those which would otherwise have been considered the next line of therapy by the treating clinician, or aided in a decision between multiple different therapy options under consideration. These results emphasize the importance of multiple data types, including expression information, to personalize treatment. We also observe that, in addition to positioning for trials or identifying cases for off-label treatment, choice of standard of care therapies is an important use of genomic data. Overall, our data supports the integration of whole genome and RNA sequencing data in the clinic, with implications both for cancer research and treatment, and ultimately the potential to improve cancer outcomes. Citation Format: Alexandra K. Bohm, Erin Pleasance, Emma Tittmus, Kathleen Wee, Gregory Taylor, Melika Bonakdar, Yaoqing Shen, Laura Williamson, Veronika Csizmok, Martin Jones, Jessica Nelson, Balvir Deol, Caralyn Reisle, Karen Mungall, Eric Chuah, Andrew Mungall, Richard Moore, Sophie Sun, Howard Lim, Daniel Renouf, Steven Jones, Marco Marra, Janessa Laskin. Personalized therapy choice integrating genome and expression data in advanced cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 98.

Purpose: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of solid tumors with dramatic and durable responses seen across multiple tumor types. However, identifying patients who will respond to these drugs remains challenging, particularly in the context of advanced and previously treated cancers. Experimental Design: We characterized fresh tumor biopsies from a heterogeneous pan-cancer cohort of 98 patients with metastatic predominantly pretreated disease through the Personalized OncoGenomics program at BC Cancer (Vancouver, Canada) using whole genome and transcriptome analysis (WGTA). Baseline characteristics and follow-up data were collected retrospectively. Results: We found that tumor mutation burden, independent of mismatch repair status, was the most predictive marker of time to progression (P = 0.007), but immune-related CD8(+) T-cell and M1-M2 macrophage ratio scores were more predictive for overall survival (OS; P = 0.0014 and 0.0012, respectively). While CD274 [programmed death-ligand 1 (PD-L1)1 gene expression is comparable with protein levels detected by IHC, we did not observe a clinical benefit for patients with this marker. We demonstrate that a combination of markers based on WGTA provides the best stratification of patients (P = 0.00071, OS), and also present a case study of possible acquired resistance to pembrolizumab in a patient with non-small cell lung cancer. Conclusions: Interpreting the tumor-immune interface to predict la efficacy remains challenging. WGTA allows for identification of multiple biomarkers simultaneously that in combination may help to identify responders, particularly in the context of a heterogeneous population of advanced and previously treated cancers, thus precluding tumor type-specific testing.

Advanced and metastatic tumors with complex treatment histories drive cancer mortality. Here we describe the POG570 cohort, a comprehensive whole-genome, transcriptome and clinical dataset, amenable for exploration of the impacts of therapies on genomic landscapes. Previous exposure to DNA-damaging chemotherapies and mutations affecting DNA repair genes, including POLQ and genes encoding Polζ, were associated with genome-wide, therapy-induced mutagenesis. Exposure to platinum therapies coincided with signatures SBS31 and DSB5 and, when combined with DNA synthesis inhibitors, signature SBS17b. Alterations in ESR1, EGFR, CTNNB1, FGFR1, VEGFA and DPYD were consistent with drug resistance and sensitivity. Recurrent noncoding events were found in regulatory region hotspots of genes including TERT, PLEKHS1, AP2A1 and ADGRG6. Mutation burden and immune signatures corresponded with overall survival and response to immunotherapy. Our data offer a rich resource for investigation of advanced cancers and interpretation of whole-genome and transcriptome sequencing in the context of a cancer clinic.

We report a case of early-onset pancreatic ductal adenocarcinoma in a patient harboring biallelic MUTYH germline mutations, whose tumor featured somatic mutational signatures consistent with defective MUTYH-mediated base excision repair and the associated driver KRAS transversion mutation p.Gly12Cys. Analysis of an additional 730 advanced cancer cases (N = 731) was undertaken to determine whether the mutational signatures were also present in tumors from germline MUTYH heterozygote carriers or if instead the signatures were only seen in those with biallelic loss of function. We identified two patients with breast cancer each carrying a pathogenic germline MUTYH variant with a somatic MUTYH copy loss leading to the germline variant being homozygous in the tumor and demonstrating the same somatic signatures. Our results suggest that monoallelic inactivation of MUTYH is not sufficient for C:G>A:T transversion signatures previously linked to MUTYH deficiency to arise (N = 9), but that biallelic complete loss of MUTYH function can cause such signatures to arise even in tumors not classically seen in MUTYH-associated polyposis (N = 3). Although defective MUTYH is not the only determinant of these signatures, MUTYH germline variants may be present in a subset of patients with tumors demonstrating elevated somatic signatures possibly suggestive of MUTYH deficiency (e.g., COSMIC Signature 18, SigProfiler SBS18/SBS36, SignatureAnalyzer SBS18/SBS36).

Objective: Advanced/recurrent gynecologic malignancies are a heterogeneous group of cancers with limited treatment options lacking predictive biomarkers. The personalized oncogenomics program (POG) is a British Columbia cancer investigational program that performs whole genome and transcriptome sequencing (WGTS) of recurrent cancers. A tumor board identifies potentially predictive and actionable biomarkers. We analyzed the discussed actionable items and their impact on treatment decisions among patients with recurrent gynecologic cancers.

PURPOSE This study investigated therapeutic potential of integrated genome and transcriptome profiling of metastatic sarcoma, a rare but extremely heterogeneous group of aggressive mesenchymal malignancies with few systemic therapeutic options. METHODS Forty-three adult patients with advanced or metastatic non-GI stromal tumor sarcomas of various histology subtypes who were enrolled in the Personalized OncoGenomics program at BC Cancer were included in this study. Fresh tumor tissues along with blood samples underwent whole-genome and transcriptome sequencing. RESULTS The most frequent genomic alterations in this cohort are large-scale structural variation and somatic copy number variation. Outlier RNA expression as well as somatic copy number variations, structural variations, and small mutations together suggest the presence of one or more potential therapeutic targets in the majority of patients in our cohort. Point mutations or deletions in known targetable cancer genes are rare; for example, tuberous sclerosis complex 2 provides a rationale for targeting the mammalian target of rapamycin pathway, resulting in a few patients with exceptional clinical benefit from everolimus. In addition, we observed recurrent 17p11-12 amplifications, which seem to be a sarcoma-specific event. This may suggest that this region harbors an oncogene(s) that is significant for sarcoma tumorigenesis. Furthermore, some sarcoma tumors carrying a distinct mutational signature suggestive of homologous recombination deficiency seem to demonstrate sensitivity to double-strand DNA-damaging agents. CONCLUSION Integrated large-scale genomic analysis may provide insights into potential therapeutic targets as well as novel biologic features of metastatic sarcomas that could fuel future experimental and clinical research and help design biomarker-driven basket clinical trials for novel therapeutic strategies.

: The threespine stickleback is a geographically widespread and ecologically highly diverse fish that has emerged as a powerful model system for evolutionary genomics and developmental biology. Investigations in this species currently rely on a single high-quality reference genome, but would benefit from the availability of additional, independently sequenced and assembled genomes. We present here the assembly of four new stickleback genomes, based on the sequencing of microfluidic partitioned DNA libraries. The base pair lengths of the four genomes reach 92-101% of the standard reference genome length. Together with their de novo gene annotation, these assemblies offer a resource enhancing genomic investigations in stickleback. The genomes and their annotations are available from the Dryad Digital Repository (https://doi.org/10.5061/dryad.113j3h7).

Hepatitis C virus (HCV) infects 180 million people worldwide and over 4 million people in the United States. HCV infection is a major cause of chronic liver disease and is recognized as a risk factor for clinical cardiovascular disease (CVD). Many studies have shown increased prevalence of cardiac and inflammatory biomarkers in patients with chronic HCV infection (CHC), and though these markers may be used to risk stratify people for cardiac disease in the general population their role in the HCV population is unknown. Patients with CHC have elevated cardiac and inflammatory biomarkers compared to noninfected controls which may play a role in CVD risk stratification. We undertook a systematic review of inflammatory and cardiac biomarkers in people with HCV infection with a focus on the effect of CHC on serum levels of these markers and their utility as predictors of CVD in this population. Medline, EMBASE, and Cochrane databases were searched for relevant articles until June 2019. A total of 2430 results were reviewed with 115 studies included. Our review revealed that HCV infection significantly alters serum levels of markers of inflammation, endothelial function, and cardiac dysfunction prior to HCV treatment, and some of which may change in response to HCV therapy. Current risk stratification tools for development of CVD in the general population may not account for the increased inflammatory markers that appear to be elevated among HCV-infected patients contributing to increased CVD risk.

The Steller sea lion is the largest member of the Otariidae family and is found in the coastal waters of the northern Pacific Rim. Here, we present the Steller sea lion genome, determined through DNA sequencing approaches that utilized microfluidic partitioning library construction, as well as nanopore technologies. These methods constructed a highly contiguous assembly with a scaffold N50 length of over 14 megabases, a contig N50 length of over 242 kilobases and a total length of 2.404 gigabases. As a measure of completeness, 95.1% of 4104 highly conserved mammalian genes were found to be complete within the assembly. Further annotation identified 19,668 protein coding genes. The assembled genome sequence and underlying sequence data can be found at the National Center for Biotechnology Information (NCBI) under the BioProject accession number PRJNA475770.

Introduction Lymphoid cancers are a biologically diverse group of neoplasms. Disease aetiology is multifactorial, implicating viral and infectious agents, immune dysfunction, and genetic factors. Lymphoid cancers affect domestic and laboratory animals; among members of Mustelidae, lymphoma has been reported in domestic ferrets, yet rarely in sea otters, with only 3 reported cases since 2002. However, since 2006, 3 sea otters at the Vancouver Aquarium (British Columbia, Canada) developed lymphoma. All 3 sea otters were rescued as young animals and have lived at the aquarium for the majority of their lives. A 21 year old female was diagnosed with chronic lymphocytic leukaemia, while 2 males, aged 12 and 16, were diagnosed with lymphoma. Both males received chemotherapy before being humanely euthanized due to declining quality of life. A high rate of blood cancers in this population motivated the molecular characterisation of the most recent lymphoma. Material and methods Whole genome sequencing was performed on peripheral blood and a lymphoma needle biopsy. The tumour biopsy was sequenced on the Illumina HiSeq X and Oxford Nanopore MinION, generating 264.5 and 4.63 passed filtered Gbp, respectively. De novo assembly was performed on the Illumina DNA and RNA data using ABySS 1.3.4. Structural variants were called with trans-abyss 1.4.10. Somatic variants were called by Strelka (v1.0.15) using matched tumour-normal samples aligned against the Enhydra lutris kenyoni reference genome. Variants were annotated by snpEFF (v4.3) using an in-house custom gene annotation database. The mutations in the sea otter tumour were subsequently compared to human and canine lymphomas. Results and discussions The sea otter genome contains 24 129 genes, of which 17 421 were mapped to the human genome. We identified several mutated genes with a known involvement in human lymphomas. We observed a stop-gain mutation in EP400, a paralog of human EP300. EP300 is a tumour suppressor which has been previously implicated in human Diffuse Large B-Cell and Follicular lymphomas. We also observed an indel in SPEN, a NOTCH pathway regulator, the deregulation of which is associated with human hematopoietic neoplasms. Conclusion These observations suggest gene and pathway deregulation are a shared genetic commonality between sea otter and human lymphomas. Comparing the mutational spectrum in human, canine, and sea otter lymphoid cancers may elucidate aetiology and treatment options, and facilitate a One Health approach to neoplasia.

Plant diseases caused by fungi and Oomycetes represent worldwide threats to crops and forest ecosystems. Effective prevention and appropriate management of emerging diseases rely on rapid detection and identification of the causal pathogens. The increase in genomic resources makes it possible to generate novel genome-enhanced DNA detection assays that can exploit whole genomes to discover candidate genes for pathogen detection. A pipeline was developed to identify genome regions that discriminate taxa or groups of taxa and can be converted into PCR assays. The modular pipeline is comprised of four components: (1) selection and genome sequencing of phylogenetically related taxa, (2) identification of clusters of orthologous genes, (3) elimination of false positives by filtering, and (4) assay design. This pipeline was applied to some of the most important plant pathogens across three broad taxonomic groups: Phytophthoras (Stramenopiles, Oomycota), Dothideomycetes (Fungi, Ascomycota) and Pucciniales (Fungi, Basidiomycota). Comparison of 73 fungal and Oomycete genomes led the discovery of 5,939 gene clusters that were unique to the targeted taxa and an additional 535 that were common at higher taxonomic levels. Approximately 28% of the 299 tested were converted into qPCR assays that met our set of specificity criteria. This work demonstrates that a genome-wide approach can efficiently identify multiple taxon-specific genome regions that can be converted into highly specific PCR assays. The possibility to easily obtain multiple alternative regions to design highly specific qPCR assays should be of great help in tackling challenging cases for which higher taxon-resolution is needed.

Thyroid-like follicular renal cell carcinoma (TLFRCC) is a rare cancer with few reports of metastatic disease. Little is known regarding genomic characteristics and therapeutic targets. We present the clinical, pathologic, genomic, and transcriptomic analyses of a case of a 27-yr-old male with TLFRCC who presented initially with bone metastases of unknown primary. Genomic DNA from peripheral blood and metastatic tumor samples were sequenced. A transcriptome of 280 million sequence reads was generated from the same tumor sample. Tumor somatic expression profiles were analyzed to detect aberrant expression. Genomic and transcriptomic data sets were integrated to reveal dysregulation in pathways and identify potential therapeutic targets. Integrative genomic analysis with The Cancer Genome Atlas (TCGA) data set revealed the following outliers in gene expression profiles: CDK6 (81st percentile), MYC (99th percentile), AR (100th percentile), PDGFRA and PDGFRB (99th and 100th percentiles, respectively), and MAP2K2 (86th percentile). The patient received first-line sunitinib to target PDGFRA and PDGFRB and had stable disease for >6 mo, followed by nivolumab upon progression. To the authors' knowledge, this is the first reported case of comprehensive somatic genomic analyses in a patient with metastatic TLFRCC. Somatic analyses provided molecular confirmation of the primary site of cancer and potential therapeutic strategies in a rare disease with little evidence of efficacy on systemic therapy.

Soil is an important reservoir for Listeria monocytogenes, a foodborne pathogen implicated in numerous produce-related outbreaks. Our objectives were to (i) compare the survival of L. monocytogenes among three soils, (ii) compare the native bacterial communities across these soils, and (iii) investigate relationships between L. monocytogenes survival, native bacterial communities, and soil properties. Listeria spp. populations were monitored on PALCAM agar in three soils inoculated with L. monocytogenes (∼5 × 106 CFU/g): conventionally farmed (CS), grassland transitioning to conventionally farmed (TS), and uncultivated grassland (GS). Bacterial diversity of the soils was analyzed using 16S rRNA targeted amplicon sequencing. A 2 log reduction of Listeria spp. was observed in all soils within 10 days, but at a significantly lower rate in GS (Fisher's least significant difference test; p < 0.05). Survival correlated with increased moisture and a neutral pH. GS showed the highest microbial diversity. Acidobacteria was the dominant phylum differentiating CS and TS from GS, and was negatively correlated with pH, carbon, nitrogen, and moisture. High moisture content and neutral pH are likely to increase the ability of L. monocytogenes to persist in soil. This study confirmed that native bacterial communities and short-term survival of L. monocytogenes varies across soils.

Metastatic adenoid cystic carcinomas (ACCs) can cause significant morbidity and mortality. Because of their slow growth and relative rarity, there is limited evidence for systemic therapy regimens. Recently, molecular profiling studies have begun to reveal the genetic landscape of these poorly understood cancers, and new treatment possibilities are beginning to emerge. The objective is to use whole-genome and transcriptome sequencing and analysis to better understand the genetic alterations underlying the pathology of metastatic and rare ACCs and determine potentially actionable therapeutic targets. We report five cases of metastatic ACC, not originating in the salivary glands, in patients enrolled in the Personalized Oncogenomics (POG) Program at the BC Cancer Agency. Genomic workup included whole-genome and transcriptome sequencing, detailed analysis of tumor alterations, and integration with existing knowledge of drug–target combinations to identify potential therapeutic targets. Analysis reveals low mutational burden in these five ACC cases, and mutation signatures that are commonly observed in multiple cancer types. Notably, the only recurrent structural aberration identified was the well-described MYB-NFIB fusion that was present in four of five cases, and one case exhibited a closely related MYBL1-NFIB fusion. Recurrent mutations were also identified in BAP1 and BCOR, with additional mutations in individual samples affecting NOTCH1 and the epigenetic regulators ARID2, SMARCA2, and SMARCB1. Copy changes were rare, and they included amplification of MYC and homozygous loss of CDKN2A in individual samples. Genomic analysis revealed therapeutic targets in all five cases and served to inform a therapeutic choice in three of the cases to date.