NHS North Thames Genomic Medicine Service’s Post

Last week, not one but two Royal Marsden initiatives were shortlisted in the prestigious #HSJAwards. 🏆 The #HSJAwards continue to be the most esteemed accolade of healthcare service excellence in the UK. The 2024 Awards will not only adhere to their 43-year-old values of sharing best practice, improving patient outcomes, and innovating drivers of better service, but will most importantly provide a well-deserved thanks to the sector. We are delighted to see the lung circulating tumour DNA project shortlisted in the Modernising Diagnostics category. 🔬 This NHS England commissioned pilot study aims to evaluate how liquid biopsy testing can be brought into an established NHS lung cancer diagnostic pathway. Liquid biopsy tests, also known as circulating tumour DNA (ctDNA) tests, sequence fragments of tumour DNA that are released into the blood stream. While this type of genetic testing is an established technology, currently no national healthcare services offer ctDNA in mainstream testing, making this a world first. Based on Guardant Health’s leading and innovative liquid biopsy technology, the Marsden360 service means that tests are analysed onsite in our state-of-the-art liquid biopsy testing facility, which is part of the North Thames Genomic Medicine Service. The Marsden360 testing facility has capacity to annually test 5,000 patients with solid tumour cancers from across England, with expansion to beyond 10,000 planned in 2024/25. You can read more about the project and our partner organisations here: https://bit.ly/4cv6U9Q

"Genomics is the diagnosis, and the most powerful argument for its universal use is that every patient afflicted with cancer deserves a full diagnosis." I am a huge advocate for universal genomic (both germline and somatic) testing and am rooting to see this happen for all solid tumor cancers in the next five years. In this recently published Journal of Clinical Oncology article, Dr Vivek Subbiah, MD and Dr. Razelle Kurzrock share their arguments on why both UGT and tumor genomic testing are needed to win the war against cancer -- doubling down on what could be perceived as controversial -- that genomics IS the diagnosis. While I'm not sure we'll ever move away from anatomical pathology and biopsy for a definitive solid tumor cancer diagnosis... ... I DO agree that every cancer patient deserves a diagnosis comprehensive of histological + somatic multigene + germline multigene findings and that medicare and private payers should follow suit. https://lnkd.in/gpqw65Sn

Check out Hamzeh's new paper! It's a super interesting insight into mismatch repair-deficient colon cancer evolution which sparked multiple related lines of work in Marnix Jansen's lab, including my PhD project. It's great to see this study published :)

Transforming Colorectal Cancer Care with NGS Testing Colorectal cancer remains one of the leading causes of cancer-related deaths worldwide. However, Next-Generation Sequencing (NGS) advances are reshaping the diagnosis and treatment landscape, offering hope for better outcomes and personalized care. Why NGS Matters in Colorectal Cancer: Precision Medicine: NGS, the epitome of Precision Medicine, delves deep into the genetic mutations fueling an individual’s cancer. This level of insight empowers oncologists to craft treatments that precisely target these mutations, instilling confidence in the effectiveness and personalization of therapy. Early Detection and Prevention: By identifying genetic predispositions and mutations early, NGS can aid in the early detection of colorectal cancer, significantly improving the chances of successful treatment and prevention strategies. Monitoring Disease Progression: NGS enables continuous monitoring of genetic changes in cancer cells, helping to track disease progression and adapt treatment plans in real-time to combat resistance. Broad Genetic Profiling: Unlike traditional methods, NGS can analyze multiple genes simultaneously, providing a comprehensive view of the tumor’s genetic landscape. This holistic approach facilitates the discovery of actionable mutations that might be missed otherwise. Enhanced Clinical Trials: Identifying specific genetic markers through NGS can match patients with clinical trials that are best suited to their genetic profiles, accelerating the development of new, targeted therapies. The Future is Now: With NGS, we are not only improving current treatment options but also paving the way for groundbreaking discoveries in colorectal cancer care. The integration of genomics into routine clinical practice is setting new standards in precision medicine, offering a beacon of hope for patients and families. Together, let's push the boundaries of what’s possible. #ColorectalCancer #NGSTesting #PrecisionMedicine #Genomics #CancerCare #Oncology #HealthcareInnovation #CancerResearch #PersonalizedMedicine #MedicalBreakthroughs #FutureOfHealthcare #EarlyDetection #ClinicalTrials

How do mismatch repair-deficient (MMRd) cancers trade off the evolutionary costs and benefits of elevated mutation rates? Delighted to share our paper on adaptive mutability in MMRd colorectal cancer (CRC) published today in Nature Genetics. This work was completed during my PhD at UCL Cancer Institute. Huge thanks to my PhD supervisor Marnix Jansen, all co-authors (including William Cross, Eszter Lakatos, Panagiotis Barmpoutis, Kevin Litchfield, Hugo Snippert and others), patients who made this research possible and our funders (Cancer Research UK (CRUK), Bowel Research UK, Rosetrees ). https://lnkd.in/eGbTrPgq Brief summary below. You can also see our tweetorial on this work 👇 https://lnkd.in/eP4juH8F We found that, MMRd colorectal cancers, which account for approximately 20% of all bowel cancers, can adapt their mutation rate in response to immune selection pressure. How? 🤔 : We discovered that a repeat DNA sequence (homopolymer) in the genes MSH6 and MSH3 undergoes successive frameshift and reversion mutation during MMRd tumor evolution, acting as a genetic switch. This allows MMRd tumors to fluctuate mutation rate, thereby exploiting the benefits of further increased mutability against its associated costs. Better understanding how MMRd colorectal cancers navigate immune selection pressures may allow us to develop new strategies to overcome immunotherapy resistance and better forecast treatment response.

I am excited to share my PhD work published yesterday in The Lancet Oncology on a rare pediatric cancer predisposition syndrome called constitutional mismatch repair deficiency (CMMRD). Thank you to all our incredible collaborators in The International Replication Repair Deficiency Consortium (IRRDC). We summarize clinical and tumor data on >200 CMMRD patients and >300 cancers from >40 ethnicities across 27 countries. This enabled us to: 1. Establish the prevalence of specific non-cancerous features and spectrum of malignant cancers these patients present with 2. Estimate cancer risk for primary and subsequent cancers 3. Gain insights into the mutational landscape of CMMRD cancers 4. Report the impact of a patient's germline gene on cancer presentation and overall survival with and without specific clinical interventions We hope this work provides meaningful insights into the biology of these cancers and improves therapeutic and management strategies for these patients. You can read the 50-day open access manuscript here: https://lnkd.in/grwaBNUN The Hospital for Sick Children University of Toronto

📃Scientific paper: Study of Liquid-Based Cytology Using Next-Generation Sequencing as a Liquid Biopsy Application in Patients with Advanced Oncological Disease Abstract: In patients with advanced cancer, it is necessary to detect driver mutations and genetic arrangements. If a mutation is found, targeted therapy may become an option. However, in most patients with advanced cancer, obtaining material can be challenging, and these determinations must be made based on small biopsies or cytologic samples. We analyzed the ability of liquid-based cytology to determine the mutational status in patients with advanced cancer by next-generation sequencing. We studied cytologic samples from 28 patients between 1 January 2018 and 31 December 2022. All samples were processed by next-generation sequencing using the Oncomine(®) Precision and Comprehensive Assay Panels for Solid Tumors. Eleven male and 17 female patients with a median age of 63.75 years were included. Clinical stage IV was predominant in 21 patients. Eleven patients died, and 17 survived. The DNA and RNA concentrations were 10.53 ng/µL and 13 ng/µL, respectively. Eleven patients showed actionable mutations, and 17 showed other genomic alterations. Liquid-based cytology can be used as a component of liquid biopsy, as it allows the identification of actionable mutations in patients with advanced oncological disease. Our findings expand the utility of liquid biopsy from different body fluids or cell aspirates. Continued on ES/IODE ➡️ https://etcse.fr/Ji8TQ ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: Personalised Risk Prediction in Hereditary Breast and Ovarian Cancer: A Protocol for a Multi-Centre Randomised Controlled Trial Abstract: SIMPLE SUMMARY: Women with disease-causing gene changes (faults/mutations) in BRCA1, BRCA2, PALB2, CHEK2 and ATM are at an increased risk of developing certain types of cancer—specifically breast (all genes) and epithelial ovarian cancer (only BRCA1, BRCA2, PALB2). At present, the risk estimates given to women by most healthcare professionals are broad (e.g., 35–85% lifetime risk of breast cancer for BRCA1 and BRCA2) and are not personalised. This can make it difficult for women to make informed decisions regarding the risk-management options available to them. By combining information about genetic, lifestyle and hormonal risk factors, we can produce a narrower, more personalised risk estimate (e.g., 44% lifetime risk of breast cancer). In this study, we aim to test whether offering personalised risk estimates to women undergoing predictive testing in genetics centres in the UK and USA better supports women’s mental health and choices about their clinical care, relative to standard care. In addition, we will explore the experiences of both staff and women taking part in the study, to understand whether personalised risk estimates are acceptable, feasible and cost-effective for use in clinical care. ABSTRACT: Women who test positive for an inherited pathogenic/likely pathogenic gene variant in BRCA1, BRCA2, PALB2, CHEK2 and ATM are at an increased risk of developing certain types of cancer—specifically breast (all) and epithelial ovarian cancer (only BRCA1, BRCA2, PAL... Continued on ES/IODE ➡️ https://etcse.fr/5DN ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: Personalised Risk Prediction in Hereditary Breast and Ovarian Cancer: A Protocol for a Multi-Centre Randomised Controlled Trial Abstract: SIMPLE SUMMARY: Women with disease-causing gene changes (faults/mutations) in BRCA1, BRCA2, PALB2, CHEK2 and ATM are at an increased risk of developing certain types of cancer—specifically breast (all genes) and epithelial ovarian cancer (only BRCA1, BRCA2, PALB2). At present, the risk estimates given to women by most healthcare professionals are broad (e.g., 35–85% lifetime risk of breast cancer for BRCA1 and BRCA2) and are not personalised. This can make it difficult for women to make informed decisions regarding the risk-management options available to them. By combining information about genetic, lifestyle and hormonal risk factors, we can produce a narrower, more personalised risk estimate (e.g., 44% lifetime risk of breast cancer). In this study, we aim to test whether offering personalised risk estimates to women undergoing predictive testing in genetics centres in the UK and USA better supports women’s mental health and choices about their clinical care, relative to standard care. In addition, we will explore the experiences of both staff and women taking part in the study, to understand whether personalised risk estimates are acceptable, feasible and cost-effective for use in clinical care. ABSTRACT: Women who test positive for an inherited pathogenic/likely pathogenic gene variant in BRCA1, BRCA2, PALB2, CHEK2 and ATM are at an increased risk of developing certain types of cancer—specifically breast (all) and epithelial ovarian cancer (only BRCA1, BRCA2, PAL... Continued on ES/IODE ➡️ https://etcse.fr/5DN ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: Hypoxia‐induced polypoid giant cancer cells in glioma promote the transformation of tumor‐associated macrophages to a tumor‐supportive phenotype Abstract: AIMS: Polypoid giant cancer cells (PGCCs) represent a unique subgroup of stem‐like cells, acting as a critical factor in promoting the recurrence of various solid tumors. The effect of PGCCs on the tumor malignancy of glioma and its immune microenvironment remains unclear. METHODS: Bioinformatic analysis was performed to investigate the relationship between M2 tumor‐associated macrophages (TAMs) infiltration and survival of glioblastoma (GBM) patients. The spatial location of M2 TAMs in GBM was also investigated using the Ivy Glioblastoma Atlas Project (Ivy GAP) database. PGCCs were quantified in glioma of different grades. CoCl(2) was used to induce PGCCs in cultures of A172 cells. PGCCs, and their progeny cells in cultures were further evaluated for morphological features, tumorsphere formation, and TAMs activation. RESULTS: The magnitude of M2 TAMs infiltration is significantly correlated with poor survival in GBM patients. M2 TAMs were enriched in the perinecrotic zone (PNZ) of GBM and positively correlated with hypoxic levels. Increased PGCCs were detected in glioma specimens of higher grades. CoCl(2) induced hypoxia and the transformation of A172 cultures into PGCCs, producing the progeny cells, PGCCs‐Dau, through asymmetric division. PGCCs and PGCCs‐Dau possessed tumor stem cell‐like features, while PGCCs‐Dau enhanced the polarization of TAMs into an M2 phenotype with relevance to immunosuppression and malignancy in GBM. CONCLUSIONS: PGCCs promote maligna... Continued on ES/IODE ➡️ https://etcse.fr/aOztr ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.