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PubMed2025

Mainstreaming of clinical genetic testing: A conceptual framework.

PURPOSE: Demand for genetic testing is increasing across medicine, whereas the genetics workforce remains stable. In response, mainstreaming models are being introduced, in which nongeneticist clinicians are increasingly involved in the genetic testing pathway. Because a standardized approach would facilitate evaluation and optimal patient care, a unified framework is warranted. METHODS: Through a focus group with clinical genetics experts, a conceptual framework for the mainstreaming of clinical genetic testing is proposed. Through a consensus process, experts elucidated the steps in the diagnostic care pathway and defined a set of variables that influence which mainstreaming model is best suited to specific patient care scenarios. RESULTS: A total of 35 individuals representing 20 distinct clinical genetics services and all Canadian provinces participated in the development of the framework. The framework describes 4 generalizable mainstreaming models of care, each with varying levels of involvement of the clinical genetics service in the diagnostic care pathway. CONCLUSION: This framework will help guide clinical teams in the design and evaluation of mainstreaming efforts. It is critical that these programs are evaluated and shared in a standardized way so that we can implement strategies that allow optimal utilization of genetics resources and improve patient care.

Humans↗
PubMed2026

The work of specialist nurses in the mainstreaming of germline genomic testing in cancer: an investigation.

BACKGROUND: Specialist nurses are increasingly working in the mainstreaming of germline genomic testing in cancer. AIMS: The study aimed to investigate the work of specialist nurses in the mainstreaming of germline genomic testing in cancer, with a focus on Lynch syndrome, and to consider the future of genomics in nursing. METHODS: Semi-structured interviews were conducted with a purposive sample of 12 specialist nurses and three genetic counsellors, and thematic analysis was carried out. FINDINGS: Prominent themes arising from the data were: the capability and capacity of specialty-based clinical nurse specialists, for whom genomics is an added part of their wider role, to deliver genomic testing; and whether these specialty-based nurses or specialist genomic nurses, who work only in genomics, are best placed to deliver genomic testing. CONCLUSION: When planning service provision in the mainstreaming of genetic testing, the capacity and capability of specialty-based clinical nurse specialists should be considered alongside the possible need for specialist genomic nurses.

Humans↗
PubMed2026

(Re)imagining the Future of Genetic Counseling: A Reflexive Qualitative Analysis of Sociopolitical Power, Cultural Safety, Systemic Racism, and Comparative Practice in the United Kingdom, Aotearoa New Zealand and, Australia.

Genetic counseling is undergoing a rapid transformation as genomic medicine becomes embedded within mainstream healthcare systems. At the same time, the profession is being challenged to respond to systemic racism, colonial legacies, technological change, and evolving expectations regarding equity and justice. Historically, genetic counseling emerged within twentieth-century medical genetics and was influenced by political, social, scientific, and medical forces that included eugenic ideology, values, and practices. The profession has since evolved substantially toward psychosocial, patient-centered, and non-directive models of care. Contemporary debates regarding "newgenics" or "neugenics" further demonstrate how concerns regarding equity, reproductive ethics, disability, and genomic stratification continue to shape genomic healthcare discourse. This qualitative reflexive practice paper explores how systemic racism, colonial legacy, cultural safety and structural power shape genetic counseling practice in the United Kingdom (UK), Aotearoa New Zealand and Australia, and how these forces continue to reshape the profession's future identity. A reflexive, narrative, and comparative qualitative approach was employed, grounded in the authors' lived professional experiences across UK and Australasian contexts and informed by purposively selected policy, professional and scholarly literature relating to cultural safety, dignity, anti-racism, and Human Rights-Based Decision-Making. Through iterative reflexive dialogue, comparative analysis, and thematic synthesis, four interrelated themes were developed examining sociopolitical context, systemic racism, cultural safety and technologization within contemporary genetic counseling practice. Comparative analysis identified substantial differences in how culturally responsive practice is conceptualized and operationalized across settings. In Aotearoa, cultural safety is strongly shaped by Te Tiriti o Waitangi, bicultural accountability, and Māori sovereignty frameworks. In Australia, culturally safer genomic care has increasingly developed through Indigenous-led initiatives and workforce reform, including the Australian Alliance for Indigenous Genomics (ALIGN). In contrast, UK practice remains largely situated within equality, diversity, and inclusion (EDI) frameworks that may insufficiently address systemic racism and structural power within increasingly diverse populations. Reflexive clinical examples demonstrated how inequities may emerge through undocumented patient values, standardized pathways, assumptions regarding autonomy, and misinterpretation of culturally specific communication styles. Re-imagining the future of genetic counseling requires more than just technological advancement. It requires reflexive engagement with dignity, inequity, and the sociopolitical realities of the populations served. These insights re-imagine a culturally grounded, socially responsive future for genetic counseling in an era shaped by genomic mainstreaming, digital transformation, artificial intelligence and workforce reform and one in which the profession remains ethically anchored, relationally attuned, and committed to justice-oriented practice.

Humans↗
PubMed2026

Prevalence of BRCA1/2 variants in an Ovarian Cancer Cohort: outcomes from a Nationwide Testing Program.

Poly(ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the management of BRCA1- and BRCA2-associated ovarian cancer (OC). In 2020, Ireland implemented a nationwide, oncology-led pathway for mainstreamed BRCA1/2 testing in patients with OC. This study evaluated the pathway and characterised the BRCA1/2 landscape in an Irish cohort of patients with OC. Samples collected between January 2020 and December 2023 were tested in two national molecular diagnostic laboratories. Single-molecule molecular inversion probe sequencing was used to detect single nucleotide variants, while multiplex ligation-dependent probe amplification assessed large genomic rearrangements. Variants were classified according to the American College of Medical Genetics and Genomics and Association for Clinical Genomic Science 2020 guidelines and CanVIG-UK specifications. In total, 535 patients were included, with a median age of 65.5 years (range, 27-89 years). Of these, 455/535 (85.0%) underwent germline BRCA1/2 (gBRCA) testing using peripheral blood, and 360/535 (67.2%) underwent tumour BRCA1/2 (tBRCA) testing, resulting in 292/535 (54.6%) patients having paired testing. Among gBRCA-tested patients, 10.3% (47/455) had a clinically actionable variant (CAV), while 2.1% (10/455) had a variant of uncertain significance. Of the 262 patients who underwent paired testing and had negative gBRCA results, 9.5% (25/262) had a somatic BRCA CAV. Recurrent germline BRCA CAVs were identified in regional clusters, including BRCA1 c.5266dup, BRCA1 c.1175_1214del, and BRCA2 c.4398_4402del. This nationwide real-world study demonstrates that mainstreamed germline and somatic BRCA1/2 testing is feasible in Ireland and reports the prevalence of BRCA CAVs in a cohort of patients with OC. Although the observed prevalence of germline BRCA CAVs was lower than anticipated, it is consistent with UK real-world data. The identification of recurrent, regionally clustered germline variants further enhances the characterisation of the Irish genomic landscape.

Journal Article↗
PubMed2026

Endodermal Organoids Along Two Axes: Single-Organ Fidelity, Inter-Organ Reconstruction, and the Unbuilt Gut-Lung Frontier.

Three-dimensional organoids of the gut, liver, and lung have become mainstream models of human development, disease, and therapy. These organs share an embryonic endodermal origin, yet the field measures their progress inconsistently because the word "maturity" carries two unrelated meanings. Herein, we review the organoid work across all three organs and propose that the two orthogonal axes of advancement be analyzed separately. The first axis is single-organ fidelity. Adult stem cell organoids are faithful but partial, reproducing the adult epithelium of their source tissue with genomic stability yet lacking stromal, vascular, immune, and neural compartments. Human pluripotent stem cell organoids are complete but immature, co-emerging with multiple lineages yet arrested in a fetal-like state. The cost of each limitation is organ-dependent, smallest in the intestine, largest for hepatic drug metabolism, and most spatially defined across the proximal and distal lungs. The second axis is inter-organ reconstruction, where progress is strongly asymmetric. The gut-liver axis is comparatively advanced and sustained by linked organoid and microphysiological systems. The gut-lung axis, by contrast, remains the least-developed frontier, and no such linked organoid has yet been built. We therefore frame it as a proposal, using in vivo and correlative evidence to outline the design principles for such a model. Four bottlenecks recur across both axes: limited vascularization; batch-to-batch variability; organ-skewed immune, microbial, and stromal microenvironments; and unidirectional signaling. We argue that benchmarking models against single-cell developmental atlases and prioritizing construction of the gut-lung frontier should guide the field over the next decade.

Intestines↗
PubMed2026

Contact tracing for hepatitis C: perspectives of people with experience of substance use and hepatitis C on intervention acceptability.

INTRODUCTION: Chronic hepatitis C (HCV) is a major cause of cirrhosis and hepatocellular carcinoma. In the UK, the principal risk factor for HCV is injecting drug use. The introduction of direct acting anti-virals (DAA's) have transformed HCV care, with cure rates of over 95%. However, HCV is often asymptomatic, and reinfection is a concern. Modelling and real-life studies demonstrate the potential effectiveness of a contact tracing approach for finding people who have acquired HCV through injecting drug use. However, it is not used routinely in the UK. This qualitative study was undertaken to assess the acceptability of a contact tracing approach to identify people who have injected drugs with an index patient recently diagnosed with HCV. METHODS: Twelve people with lived or living experience of injecting drug use and an HCV diagnosis were interviewed using semi-structured interview topic guides. Participants were purposefully selected according to the inclusion criteria and to ensure there was an even spread of male and female participants. Sekhon's Theoretical Framework of Acceptability, incorporating seven components (affective attitude, burden, ethicality, intervention coherence, opportunity cost, perceived effectiveness, and self-efficacy) was used to analyse data from interview transcripts. RESULTS: A sample of 12 people who inject drugs in the UK indicated that a contact tracing approach was acceptable across two components of Sekhon's acceptability framework: affective attitude and ethicality. Participants broadly found the idea of tracing people who may be at risk of contracting HCV acceptable, and the approach aligned with their value systems. A contact tracing approach would help alleviate concerns about putting other people's lives at risk through HCV transmission and was seen as a 'sensible' way of finding people at risk. However, there were caveats to this acceptability. Contact tracing approaches delivered by mainstream health, or governmental organisations increased burden, opportunity costs and perceived effectiveness of a contact tracing approach for HCV, particularly within contexts of exclusion and criminalisation of people who inject drugs. Burden and opportunity costs were also affected by individual experiences and risks of violence, sexual violence and abuse. There was a lack of knowledge of contact tracing approaches amongst respondents, leading to a lack of intervention coherence and misunderstandings of what contact tracing was and how it would work. Trusted relationships with NGOs and HCV specialist nurses reduced burden and increased confidence and ability (self-efficacy) to engage with a contact tracing approach. CONCLUSION: People who inject drugs broadly perceive contact tracing as an acceptable method of finding people who are at risk of HCV. However, this acceptability is based on specific modes of delivery through trusted organisations. Findings further highlight the importance of naming and describing contact tracing approaches appropriately, as well as assessing and mitigating against potential risk to index patients, to increase self-efficacy and capacity to engage. Considering these findings, the potential for expanding existing contact tracing approaches should be explored to ensure the UK reaches and maintains its elimination targets.

Humans↗
PubMed2026

Survey of diagnostic laboratories highlights need for improved standards in somatic genomic testing and reporting.

There is a growing international need to support somatic genomic testing, standardised variant curation and improved patient access to molecular profiling for somatic conditions, including cancer. We conducted a survey of scope, curation, reporting and sharing practices of diagnostic laboratories performing somatic testing in Australia and New Zealand. Laboratories with accreditation (n = 41) were invited in 2023 to complete a semi-structured, 25-question interview. Responses were received for 27 laboratories (66% response rate) offering solid tumour, haematological malignancy and non-cancer services. Only 36% of laboratories offered tests capturing the full breadth of variants, from single-nucleotide variants to gene fusions. Knowledge sharing was rare, with only one laboratory submitting variant classifications to a public knowledge base. Most laboratories (96%) conducted somatic testing in oncology. Of cancer laboratories, 35% offered testing considered capable of comprehensive genomic profiling (CGP). Almost half of cancer laboratories had already adopted the 2022 ClinGen/CGC/VICC oncogenicity guidelines, and 84% were using AMP/ASCO/CAP 2017 clinical significance guidelines. Only 47% of mixed discipline cancer laboratories reported biomarkers such as tumour mutational burden, with wide variation in reporting of matched therapy options. Our study has generated a unique overview of somatic laboratory practices in the region, and areas for global standardisation in somatic molecular testing and reporting. We also provide a model for practice and guideline uptake assessment, for application by other country-wide networks. This is particularly relevant in anticipation of CGP mainstreaming, with the increasing complexity of sequencing interpretation for laboratories and clinicians.

Humans↗
PubMed2026

The role of pathology laboratories in integrating genetic testing into Australian primary care: an implementation science perspective.

As genomic testing moves into mainstream healthcare, non-genetic healthcare professionals, including general practitioners (GPs), play a critical role as gatekeepers to genetic services. Laboratories are essential in supporting this transition by providing not only high-quality genetic tests but also point-of-care tools, educational materials and clinical guidance to support their use. This study aimed to explore how these tools and supports are conceptualized, developed, implemented and evaluated and how laboratories integrate them into their relationships with GPs, an essential process for paving the way toward better use of genomics in primary care. A qualitative study design was employed using semi-structured, in-depth interviews with representatives from genetic laboratories across Australia. The Consolidated Framework for Implementation Research (CFIR) guided deductive content analysis of data. Findings spanned the four CFIR domains (Intervention Characteristics, Outer Setting, Inner Setting and Implementation Process) across 34 constructs. Participants reported that laboratories viewed point-of-care tools and resources as essential responses to persistent genomic knowledge gaps among GPs. Development of evidence-based, practice-driven and adaptable resources was supported and rewarded within laboratory organisations. A strong culture of clinical responsibility and implementation readiness, combined with robust networks and communications, enabled timely support for GPs. Gaps identified included lack of implementation planning, misalignments between laboratory-developed resources and GPs' real-world needs and inadequate mechanisms for obtaining GPs' feedback, which made evaluation problematic. By applying an implementation science framework, these findings provide insights for future efforts to build and sustain the provision of point-of-care tools and support, ultimately improving the integration of genomics in primary care.

Journal Article↗
PubMed2026

Species identification, discovery, and biomonitoring: Strategic priorities for DNA barcoding in Europe, set in a global context.

The International Barcode of Life (iBOL) initiative is building a globally accessible DNA-based system for species identification and discovery. This paper outlines the mission and strategic priorities for the iBOL community in Europe (iBOL Europe), set in a global context. The mission of iBOL Europe is to produce, curate, and provide access to a complete DNA barcode reference library of European eukaryotic biodiversity, catalyzing species discovery and enabling comprehensive, harmonized species identification and biomonitoring, and supporting the global iBOL program. Immediate objectives include completing reference libraries for priority taxa, democratizing access to sequencing technologies, and strengthening a distributed community of practice. Key actions identified span five thematic areas: community building, sample collection and taxonomic verification, sequencing infrastructure, data management, and mainstreaming DNA-based approaches to meet societal needs. The strategy emphasizes integration with European research infrastructures to ensure long-term sustainability and resilience for biodiversity genomics in Europe.

DNA barcoding↗
PubMed2025

Hierarchical metabolic engineering for rewiring cellular metabolism.

Metabolic engineering is a key enabling technology for rewiring cellular metabolism to enhance production of chemicals, biofuels, and materials from renewable resources. However, how to make cells into efficient factories is still challenging due to its robust metabolic networks. To open this door, metabolic engineering has realized great breakthroughs through three waves of technological research and innovations, especially the third wave. To understand the third wave of metabolic engineering better, we discuss its mainstream strategies and examples of its application at five hierarchies, including part, pathway, network, genome, and cell level, and provide insights as to how to rewire cellular metabolism in the context of maximizing product titer, yield, and productivity. Finally, we highlight future perspectives on metabolic engineering for the successful development of cell factories.

Metabolic Engineering↗
PubMed2025

Exploring the causal association between television viewing and meniscal injuries: A two-sample Mendelian randomization analysis.

The aim of this study was to assess whether there is a potential causal relationship between sedentary behavior and meniscal injuries based on the Mendelian randomization (MR) method. This study used a two-sample MR design to integrate pooled data from a large-scale genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) that were significantly associated with sedentary behavior (represented by daily TV-viewing time) and independent of each other were selected as instrumental variables, while focusing on data from populations of European ancestry. To ensure the robustness and reliability of the analyses, 3 mainstream MR analysis methods were combined in this study: inverse variance weighted (IVW), weighted median estimation (WME) and MR-Egger regression. Heterogeneity test, horizontal multivariate analysis, and leave-one-out sensitivity test were also conducted to further validate the stability of causal estimation. The results of the IVW method showed that sedentary behavior was significantly associated with the risk of meniscus injury, with an OR (95% CI) of 2.93 (1.89-4.52), and a P-value of&#x2005;<&#x2005;.001, suggesting that sedentary behavior may be an important risk factor for meniscus injury. No significant bias was found in the heterogeneity test and the assessment of multiple validity, and the sensitivity analysis showed that the effect of individual SNPs on the overall estimation was small, and the results had good robustness. This study provides genetic epidemiological evidence of a positive causal effect of sedentary behavior on meniscal injuries based on a causal inference approach with genetic instrumental variables. The results suggest that reducing sedentary time, especially prolonged TV watching behavior, may reduce the risk of meniscus injury to some extent.

Humans↗
PubMed2025

Adaptive Evolution for Freshwater Adaptation in Coilia nasus by Directional Selection on Osmoregulation Genes.

The molecular mechanisms underlying the adaptation to freshwater habitats in fish of marine origin remain unclear. Grenadier anchovies, such as Coilia nasus, originate from marine environments and include both anadromous and freshwater-resident conspecifics, making them ideal for studying adaptive evolution from marine to freshwater habitats. We conducted a comparative population genomic and transcriptome analysis of two distinct C. nasus lineages, one anadromous and the other freshwater-resident, collected from mainstream and estuarine regions of the Yangtze River, China. By genome-wide genotyping of the anadromous and the freshwater-resident populations, we observed significant divergence in osmoregulation, energy metabolism, and immune response pathways associated with ecological adaptation and energy expenditure for migration. Some ion transport genes such as CAMK1, ATP1&#x3b1;3, KCNJ1 and SLC30A2 were identified that may contribute to freshwater adaptation. Notably, numerous mineralocorticoid signalling genes (e.g., NR3C2, SGK1, ATP1&#x3b1;3, KCNJ1) exhibit dynamic change between the anadromous and freshwater populations, suggesting an important role for the hormone cortisol in regulating salinity acclimation in euryhaline fish. Among these genes, the ion channel ATP1&#x3b1;3 experienced adaptive amino acid substitutions (Val317Ile and Thr329Ser), which appear to be evolutionary hotspots across migratory species based on ortholog comparisons. These variants may facilitate sodium/potassium transport and highlight salinity tolerance as a key driver of divergence in anadromous fish transitioning to freshwater. These results enhance our understanding of the genetic basis underlying freshwater adaptation for an anadromous fish across osmotic boundaries.

Animals↗
PubMed2026

A nonlinear multi-omics data integration and classification model based on pathway self-attention and graph convolutional networks.

The abundance of omics data has significantly advanced the development of multi-omics data integration techniques. Non-linear embedding approaches for data integration have gradually become the mainstream in multi-omics research, as these approaches can substantially improve cancer analysis by enhancing the quality of the embeddings. However, current multi-omics data integration methods are typically confined to omics measurements, neglecting domain-specific prior knowledge encompassing biological pathways. In this study, we proposed a multi-omics integrated classification model, PathTransGCN, based on pathway self-attention and graph convolutional networks (GCN). The model integrated biological pathway information into multi-omics data analysis with the aim of enhancing the accuracy of cancer classification. Multi-omics data for breast cancer (BRCA), non-small cell lung cancer (NSCLC), and low-grade glioma (LGG) were obtained from The Cancer Genome Atlas (TCGA) and UCSC Xena databases. These data included gene mutations, DNA methylation, copy number variations, and gene expression, and were used to assess the model's generalizability across different cancers. First, PathTransGCN employed a pathway self-attention module to learn latent representations of samples across different pathways, thereby obtaining multi-omics integration vectors. Concurrently, a patient similarity network (PSN) was constructed using the similarity network fusion (SNF) approach. Second, the integrated vectors and the PSN were jointly fed into a GCN for end-to-end training, enabling precise classification of cancer subtypes. Through multi-omics data analysis of the BRCA dataset, PathTransGCN outperformed several popular algorithms (such as MoGCN and DeePathNet) in the five-class classification of cancer subtypes, achieving an accuracy rate of 87.6% and an F1 score of 86.4%. Moreover, the model demonstrated robust generalization capabilities across both NSCLC and LGG datasets, while effectively identifying key disease-associated biomarkers at the pathway level. Experimental results demonstrate that PathTransGCN exhibits outstanding performance in integrating omics data and delivering interpretable classification outcomes, presenting significant potential for clinical applications.

Humans↗
PubMed2026

Automated Classification of Lymphoma Subtypes From Histopathological Images Using a U-Net Deep Learning Model: Comparative Evaluation Study.

BACKGROUND: Accurate classification and grading of lymphoma subtypes are essential for treatment planning. Traditional diagnostic methods face challenges of subjectivity and inefficiency, highlighting the need for automated solutions based on deep learning techniques. OBJECTIVE: This study aimed to investigate the application of deep learning technology, specifically the U-Net model, in classifying and grading lymphoma subtypes to enhance diagnostic precision and efficiency. METHODS: In this study, the U-Net model was used as the primary tool for image segmentation integrated with attention mechanisms and residual networks for feature extraction and classification. A total of 620 high-quality histopathological images representing 3 major lymphoma subtypes were collected from The Cancer Genome Atlas and the Cancer Imaging Archive. All images underwent standardized preprocessing, including Gaussian filtering for noise reduction, histogram equalization, and normalization. Data augmentation techniques such as rotation, flipping, and scaling were applied to improve the model's generalization capability. The dataset was divided into training (70%), validation (15%), and test (15%) subsets. Five-fold cross-validation was used to assess model robustness. Performance was benchmarked against mainstream convolutional neural network architectures, including fully convolutional network, SegNet, and DeepLabv3+. RESULTS: The U-Net model achieved high segmentation accuracy, effectively delineating lesion regions and improving the quality of input for classification and grading. The incorporation of attention mechanisms further improved the model's ability to extract key features, whereas the residual structure of the residual network enhanced classification accuracy for complex images. In the test set (N=1250), the proposed fusion model achieved an accuracy of 92% (1150/1250), a sensitivity of 91.04% (1138/1250), a specificity of 89.04% (1113/1250), and an F1-score of 90% (1125/1250) for the classification of the 3 lymphoma subtypes, with an area under the receiver operating characteristic curve of 0.95 (95% CI 0.93-0.97). The high sensitivity and specificity of the model indicate strong clinical applicability, particularly as an assistive diagnostic tool. CONCLUSIONS: Deep learning techniques based on the U-Net architecture offer considerable advantages in the automated classification and grading of lymphoma subtypes. The proposed model significantly improved diagnostic accuracy and accelerated pathological evaluation, providing efficient and precise support for clinical decision-making. Future work may focus on enhancing model robustness through integration with advanced algorithms and validating performance across multicenter clinical datasets. The model also holds promise for deployment in digital pathology platforms and artificial intelligence-assisted diagnostic workflows, improving screening efficiency and promoting consistency in pathological classification.

Humans↗
PubMedDate not supplied

Nature and fate of insecticide residues inhaled by rats in cigarette smoke.

Radioactive carbaryl, carbofuran, parathion, leptophos, and DDT were added to cigarettes and the mainstream smoke was directed to the lungs of rats via the trachea. Total radiocarbon transfer to the lungs ranged from 9 to 15% of that in the tobacco burned during a smoking process involving eight 5-ml puffs. Exhalation of 14C residues during this time was 24 to 30% of that inhaled with all insecticides except carbofuran, of which 42% of the residues was exhaled. After 5 hr, total exhalation of the consumed radiocarbon was 35% for parathion, 65% for carbofuran, and approximately 50% for the other products. The nature of the 14C residues inhaled, their urinary and fecal excretion, and their deposition in and dissipation from various organs and tissues are presented.

Animals↗
PubMed2026

Uptake of germline testing for Lynch Syndrome in patients with deficient mismatch repair/ microsatellite-high colorectal cancer in the public hospital system in South Australia.

Lynch syndrome (LS) accounts for approximately 4% of colorectal cancer (CRC) cases and arises from pathogenic variants in mismatch repair (MMR) genes. Australian guidelines recommend universal MMR or microsatellite instability (MSI) screening in all CRC patients; however, real-world uptake remains variable. This study evaluated rates of MMR/MSI screening, germline testing, and genetics referrals across two major public hospitals in South Australia. A retrospective review of 1775 patients discussed at colorectal multidisciplinary team meetings in the Royal Adelaide and Queen Elizabeth hospitals between January 2021 and December 2023 was conducted to identify rates of MMR/MSI screening and subsequent referral of eligible patients to genetics. Of the 1129 colorectal cancer cases identified, MMR/MSI testing was performed in 93.2% (1052/1129), with deficiency detected in 12.5% (131/1052). Of these, 37% (49/131) were eligible for genetics referral after exclusion of somatic causes. Among eligible patients, 73.5% (36/49) were referred, and 43% (21/49) underwent germline testing. LS was confirmed in 12 patients (9% of deficient MMR CRC), while 9 patients (6.9%) were classified as having Lynch-like syndrome. Despite high screening rates, gaps remain in genetics referral and testing. Barriers included lack of reflex testing, loss to follow-up, and patient refusal. Targeted system-level interventions and improved genomic education are needed to enhance adherence to guidelines and optimise patient outcomes.

Humans↗