The expanding global genomics landscape: Converging priorities from national genomics programs DOI Creative Commons

Caitlin Howley,

Matilda Haas,

Wadha A. Al Muftah

et al.

The American Journal of Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

SummaryThe global landscape of health genomics is expanding rapidly, with an increasing number national and international initiatives, many which are targeted toward accelerating the clinical implementation genomic technologies services in context local systems. This includes a range entities different levels maturity, funding sources, strategies that focus on research priorities to varying degrees. While there no "one-size-fits-all" approach, analysis programs helps identify common priority areas, barriers, enablers. Here, we synthesize converging several highlight importance progressing scale.Graphical abstract

Language: Английский

Implementing Whole Genome Sequencing (WGS) in Clinical Practice: Advantages, Challenges, and Future Perspectives DOI Creative Commons
Petar Brlek, Luka Bulić, Matea Bračić

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 504 - 504

Published: March 13, 2024

The integration of whole genome sequencing (WGS) into all aspects modern medicine represents the next step in evolution healthcare. Using this technology, scientists and physicians can observe entire human comprehensively, generating a plethora new data. Modern computational analysis entails advanced algorithms for variant detection, as well complex models classification. Data science machine learning play crucial role processing interpretation results, using enormous databases statistics to discover support current genotype–phenotype correlations. In clinical practice, technology has greatly enabled development personalized medicine, approaching each patient individually accordance with their genetic biochemical profile. most propulsive areas include rare disease genomics, oncogenomics, pharmacogenomics, neonatal screening, infectious genomics. Another application WGS lies field multi-omics, working towards complete biomolecular Further technological technologies led birth third fourth-generation sequencing, which long-read single-cell nanopore sequencing. These technologies, alongside continued implementation medical research show great promise future medicine.

Language: Английский

Citations

37
Origins and impact of extrachromosomal DNA DOI Creative Commons
Chris Bailey, Oriol Pich, Kerstin Thol

et al.

Nature, Journal Year: 2024, Volume and Issue: 635(8037), P. 193 - 200

Published: Nov. 6, 2024

Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer

Language: Английский

Citations

17
PFMG2025–integrating genomic medicine into the national healthcare system in France DOI Creative Commons
Caroline Abadie,

Aldja Abderrahmane,

Ouarda Abdous

et al.

The Lancet Regional Health - Europe, Journal Year: 2025, Volume and Issue: 50, P. 101183 - 101183

Published: Jan. 6, 2025

Summary

Integrating genomic medicine into healthcare systems is a health policy challenge that requires continuously transferring scientific advances clinics and ensuring equal access for patients. France was one of the first countries to integrate genome sequencing clinical practice at nationwide level, with ambition provide more accurate diagnostics personalized treatments. Since 2016, French government has invested €239M in 2025 Genomic Medicine Initiative (PFMG2025) which so far focused on patients rare diseases (RD), cancer genetic predisposition (CGP) cancers. PFMG2025 addressed numerous challenges set up an operational organizational framework. As December 31st 2023, 12,737 results were returned prescribers RD/CGP (median delivery time: 202 days, diagnostic yield: 30.6%) 3109 45 days). PFMG2025's future priorities encompass economic sustainability, strengthening links research, empowering practitioners, fostering collaborations European partners.

Funding

have been by government.

Language: Английский

Citations

3
Ongoing chromothripsis underpins osteosarcoma genome complexity and clonal evolution DOI Creative Commons
Jose Espejo Valle-Inclán, Solange De Noon, Katherine Trevers

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Osteosarcoma is the most common primary cancer of bone, with a peak incidence in children and young adults. Using multi-region whole-genome sequencing, we find that chromothripsis an ongoing mutational process, occurring subclonally 74% osteosarcomas. Chromothripsis generates highly unstable derivative chromosomes, evolution which drives acquisition oncogenic mutations, clonal diversification, intra-tumor heterogeneity across diverse sarcomas carcinomas. In addition, characterize new mechanism, termed loss-translocation-amplification (LTA) chromothripsis, mediates punctuated about half pediatric adult high-grade LTA occurs when single double-strand break triggers concomitant TP53 inactivation oncogene amplification through breakage-fusion-bridge cycles. It particularly prevalent osteosarcoma not detected other cancers driven by mutation. Finally, identify level genome-wide loss heterozygosity as strong prognostic indicator for osteosarcoma.

Language: Английский

Citations

2
The grand challenge of moving cancer whole-genome sequencing into the clinic DOI
Dilara Akhoundova, Mark A. Rubin

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(1), P. 39 - 40

Published: Jan. 1, 2024

Language: Английский

Citations

9
Assessing the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases DOI Creative Commons
Jonathan Mitchell, Niedzica Camacho, Patrick R. Shea

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 19, 2025

Abstract To assess the contribution of rare coding germline genetic variants to prostate cancer risk and severity, we perform here a meta-analysis 37,184 cases 331,329 male controls from five cohorts with whole exome or genome sequencing data, one cohort imputed array data. At gene level, our case-control collapsing analysis confirms associations between damaging in four genes increased risk: SAMHD1 , BRCA2 ATM at study-wide significance level ( P < 1×10 −8 ), CHEK2 suggestive threshold 2.6×10 −6 ). Our case-only analysis, reveals that AOX1 are associated more aggressive disease (OR = 2.60 [1.75–3.83], 1.35×10 as well confirming role determining severity. single-variant study missense variant TERT is substantially reduced 0.13 [0.07–0.25], 4.67×10 −10 non-synonymous further three ANO7 SPDL1 AR ) HOXB13 BIK Altogether, this work provides deeper insights into architecture biological basis potential implications for clinical prediction therapeutic strategies.

Language: Английский

Citations

1
ESMO Precision Oncology Working Group recommendations on the structure and quality indicators for molecular tumour boards in clinical practice DOI Creative Commons
C. Benedikt Westphalen,

L. Boscolo Bielo,

Philippe Aftimos

et al.

Annals of Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

With an increased uptake of genomic profiling in clinical practice and the evolving complexity diagnostic modalities, vast amounts complex data need to be properly interpreted integrated into individualised care plan. To address these challenges, molecular tumour boards (MTBs) have been widely established. As today, no international recommendations regulating composition workflows MTBs defined. ESMO's Precision Oncology Working Group (POWG) established expert panel precision oncology defined core areas interest. After several consultations through consensus process, group reached a level for each recommendation. The five components MTB process that are critical its function use: (i) primary task consists providing genomic-informed recommendations, particularly cases exhibiting alterations; (ii) achieve this, should encompass interdisciplinary expertise, with key roles oncologists pathologists training geneticists; (iii) MTBs' documented structured report includes treatment strategies, management plans potential tumour-detected germline alterations guidance additional testing; (iv) follow-up processes implemented monitoring effectiveness (v) finally, proposed quality indicators operating MTBs, including turnaround times discussion proportion which actionable trial enrolments were successfully implemented. These POWG can serve as help define standards allow harmonisation further expedite integration practice.

Language: Английский

Citations

1
A call to action to scale up research and clinical genomic data sharing DOI
Zornitza Stark, David Glazer, Oliver Hofmann

et al.

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 7, 2024

Language: Английский

Citations

8
Clinical Use of Molecular Biomarkers in Canine and Feline Oncology: Current and Future DOI Creative Commons
Heike Aupperle‐Lellbach, Alexandra Kehl, Simone de Brot

et al.

Veterinary Sciences, Journal Year: 2024, Volume and Issue: 11(5), P. 199 - 199

Published: May 2, 2024

Molecular biomarkers are central to personalised medicine for human cancer patients. It is gaining traction as part of standard veterinary clinical practice dogs and cats with cancer. can be somatic or germline genomic alterations ascertained from tissues body fluids using various techniques. This review discusses how these determined the findings used in settings diagnostic, prognostic, predictive, screening biomarkers. We showcase currently available date testing a setting, discussing their utility each biomarker class. also look at some emerging molecular that promising use. Finally, we discuss hurdles need overcome going ‘bench bedside’, i.e., translation discovery adoption by clinicians. As understand more genomics underlying canine feline tumours, will undoubtedly become mainstay delivering precision care

Language: Английский

Citations

6
High‐throughput molecular assays for inclusion in personalised oncology trials – State‐of‐the‐art and beyond DOI Creative Commons
Anders Edsjö, Hege G. Russnes, Janne Lehtiö

et al.

Journal of Internal Medicine, Journal Year: 2024, Volume and Issue: 295(6), P. 785 - 803

Published: May 2, 2024

Abstract In the last decades, development of high‐throughput molecular assays has revolutionised cancer diagnostics, paving way for concept personalised medicine. This progress been driven by introduction such technologies through biomarker‐driven oncology trials. this review, strengths and limitations various state‐of‐the‐art sequencing technologies, including gene panel (DNA RNA), whole‐exome/whole‐genome whole‐transcriptome sequencing, are explored, focusing on their ability to identify clinically relevant biomarkers with diagnostic, prognostic and/or predictive impact. includes need assess complex biomarkers, example microsatellite instability, tumour mutation burden homologous recombination deficiency, patients suitable specific therapies, immunotherapy. Furthermore, crucial role biomarker analysis multidisciplinary boards in selecting trial inclusion is discussed relation concepts, drug repurposing. Recognising that today's exploratory techniques will evolve into tomorrow's routine diagnostics clinical study assays, importance emerging multimodal as proteomics vivo sensitivity testing, also discussed. addition, key regulatory aspects patient engagement all phases a described. Finally, we propose set recommendations consideration when planning new precision medicine trial.

Language: Английский

Citations

6