Applications of Nanopore sequencing in precision cancer medicine DOI Creative Commons
Sergey A. Dyshlovoy,

Stefanie Paigin,

Ann‐Kristin Afflerbach

et al.

International Journal of Cancer, Journal Year: 2024, Volume and Issue: 155(12), P. 2129 - 2140

Published: July 19, 2024

Oxford Nanopore Technologies sequencing, also referred to as stands at the forefront of a revolution in clinical genetics, offering potential for rapid, long read, and real-time DNA RNA sequencing. This technology is currently making sequencing more accessible affordable. In this comprehensive review, we explore its regarding precision cancer diagnostics treatment. We encompass critical analysis cases where was successfully applied identify point mutations, splice variants, gene fusions, epigenetic modifications, non-coding RNAs, other pivotal biomarkers that defined subsequent treatment strategies. Additionally, address challenges applications discuss current efforts overcome them.

Language: Английский

Extrachromosomal DNA amplifications in cancer DOI
Eunhee Yi, Rocío Chamorro González, Anton G. Henssen

et al.

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(12), P. 760 - 771

Published: Aug. 11, 2022

Language: Английский

Citations

74
Long-Read DNA Sequencing: Recent Advances and Remaining Challenges DOI Creative Commons

Peter E. Warburton,

Robert Sebra

Annual Review of Genomics and Human Genetics, Journal Year: 2023, Volume and Issue: 24(1), P. 109 - 132

Published: April 19, 2023

DNA sequencing has revolutionized medicine over recent decades. However, analysis of large structural variation and repetitive DNA, a hallmark human genomes, been limited by short-read technology, with read lengths 100-300 bp. Long-read (LRS) permits routine fragments tens to hundreds kilobase pairs in size, using both real-time synthesis nanopore-based direct electronic sequencing. LRS haplotypic phasing genomes enabled the discovery characterization rare pathogenic variants repeat expansions. It also recently assembly complete, gapless genome that includes previously intractable regions, such as highly centromeres homologous acrocentric short arms. With addition protocols for targeted enrichment, epigenetic modification detection, long-range chromatin profiling, promises launch new era understanding genetic diversity mutations populations.

Language: Английский

Citations

68
FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions DOI

Masuko Katoh,

Yohann Loriot,

Giovanni Brandi

et al.

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(4), P. 312 - 329

Published: Feb. 29, 2024

Language: Английский

Citations

63
Blocking Genomic Instability Prevents Acquired Resistance to MAPK Inhibitor Therapy in Melanoma DOI Creative Commons
Prashanthi Dharanipragada, Xiao Zhang,

Sixue Liu

et al.

Cancer Discovery, Journal Year: 2023, Volume and Issue: 13(4), P. 880 - 909

Published: Jan. 26, 2023

Blocking cancer genomic instability may prevent tumor diversification and escape from therapies. We show that, after MAPK inhibitor (MAPKi) therapy in patients mice bearing patient-derived xenografts (PDX), acquired resistant genomes of metastatic cutaneous melanoma specifically amplify resistance-driver, nonhomologous end-joining (NHEJ), homologous recombination repair (HRR) genes via complex rearrangements (CGR) extrachromosomal DNAs (ecDNA). Almost all sensitive acquired-resistant harbor pervasive chromothriptic regions with disproportionately high mutational burdens significant overlaps ecDNA CGR spans. Recurrently, somatic mutations within amplicons enrich for HRR signatures, particularly tumors. Regardless sensitivity or resistance, breakpoint-junctional sequence analysis suggests NHEJ as critical to double-stranded DNA break underlying formation. In human cell lines PDXs, targeting by a DNA-PKCS prevents/delays MAPKi resistance reducing the size ecDNAs CGRs early on combination treatment. Thus, causes prevents resistance. Acquired often results heterogeneous, redundant survival mechanisms, which challenge strategies aimed at reversing Acquired-resistant melanomas recurrently evolve resistance-driving resistance-specific CGRs, thereby nominating chromothripsis-ecDNA-CGR biogenesis resistance-preventive target. Specifically, DNA-PKCS/NHEJ suppressing ecDNA/CGR MAPKi-treated melanomas. This article is highlighted Issue feature, p. 799.

Language: Английский

Citations

49
Extrachromosomal DNA in cancer DOI
Xiaowei Yan, Paul S. Mischel, Howard Y. Chang

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(4), P. 261 - 273

Published: Feb. 26, 2024

Language: Английский

Citations

29
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
Modern biology of extrachromosomal DNA: A decade-long voyage of discovery DOI Creative Commons
Qinglin Yang, Yulei Xie,

Kailiang Qiao

et al.

Cell Research, Journal Year: 2025, Volume and Issue: 35(1), P. 11 - 22

Published: Jan. 3, 2025

Abstract Genomic instability is a hallmark of cancer and major driving force tumorigenesis. A key manifestation genomic the formation extrachromosomal DNAs (ecDNAs) — acentric, circular DNA molecules ranging from 50 kb to 5 Mb in size, distinct chromosomes. Ontological studies have revealed that ecDNA serves as carrier oncogenes, immunoregulatory genes, enhancers, capable elevated transcription its cargo genes heterogeneity, leading rapid tumor evolution therapy resistance. Although was documented over half century ago, past decade has witnessed surge breakthrough discoveries about biological functions. Here, we systematically review modern biology uncovered last ten years, focusing on how during this pioneering stage illuminated our understanding ecDNA-driven transcription, progression. Furthermore, discuss ongoing efforts target novel approach therapy. This burgeoning field entering new phase, poised reshape knowledge therapeutic strategies.

Language: Английский

Citations

5
Coordinated inheritance of extrachromosomal DNAs in cancer cells DOI Creative Commons
King L. Hung, Matthew G. Jones, Ivy Tsz-Lo Wong

et al.

Nature, Journal Year: 2024, Volume and Issue: 635(8037), P. 201 - 209

Published: Nov. 6, 2024

The chromosomal theory of inheritance dictates that genes on the same chromosome segregate together while different chromosomes assort independently

Language: Английский

Citations

14
Extrachromosomal DNA in Cancer DOI Creative Commons
Vineet Bafna, Paul S. Mischel

Annual Review of Genomics and Human Genetics, Journal Year: 2022, Volume and Issue: 23(1), P. 29 - 52

Published: May 25, 2022

In cancer, complex genome rearrangements and other structural alterations, including the amplification of oncogenes on circular extrachromosomal DNA (ecDNA) elements, drive formation progression tumors. ecDNA is a particularly challenging alteration. By untethering from chromosomal constraints, it elevates oncogene copy number, drives intratumoral genetic heterogeneity, promotes rapid tumor evolution, results in treatment resistance. The profound changes shape nuclear architecture generated by alter transcriptional landscape tumors catalyzing new types regulatory interactions that do not occur chromosomes. current suite tools for interrogating cancer genomes well suited deciphering sequence but has limited ability to resolve structure dynamics generates. Here, we review challenges resolving form function discuss emerging tool kit spatial organization, what been learned date about how this dramatic change alters development, progression, drug

Language: Английский

Citations

34
eccDNA Atlas: a comprehensive resource of eccDNA catalog DOI
Tengwei Zhong, Wenqing Wang,

Houyan Liu

et al.

Briefings in Bioinformatics, Journal Year: 2023, Volume and Issue: 24(2)

Published: Feb. 9, 2023

Abstract Extrachromosomal circular DNA (eccDNA) represents a large category of non-mitochondrial and non-plasmid extrachromosomal DNA, playing an indispensable role in various aspects such as tumorigenesis, immune responses. However, the information characteristics functions about eccDNA is fragmented, hiding behind abundant literatures massive whole-genome sequencing (WGS) data, which has not been sufficiently used for identification eccDNAs. Therefore, establishing integrated repository portal essential identifying analyzing Here, we developed Atlas (http://lcbb.swjtu.edu.cn/eccDNAatlas), user-friendly database eccDNAs that aims to provide high-quality resource browsing, searching from multiple species. currently contains 629 987 8221 ecDNAs manually curated 1105 predicted by AmpliconArchitect based on WGS data involved 66 diseases, 57 tissues 319 cell lines. The content each entry includes sequence, disease, function, characteristic, validation strategies. Furthermore, annotations utilities were provided explore existing or user-defined including oncogenes, typical enhancers, super CTCF-binding sites, SNPs, chromatin accessibility, eQTLs, gene expression, survival genome visualization. Overall, provides warehouse serves important tool future research.

Language: Английский

Citations

20