4.4 Review

Extrachromosomal DNA in Cancer

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Article Oncology

Plasticity of Extrachromosomal and Intrachromosomal BRAF Amplifications in Overcoming Targeted Therapy Dosage Challenges

Kai Song et al.

Summary: Understanding the structure and dynamics of oncogene amplifications is crucial for overcoming tumor relapse. BRAF amplifications in melanoma show high plasticity under MAPKi dosage challenges, involving de novo genomic alterations even in the HSR mode. Furthermore, BRAF FA-driven, dual MAPKi-resistant cells expand the spectrum of resistance-linked ferroptosis sensitivity.

CANCER DISCOVERY (2022)

Article Oncology

Live-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in Cancer

Eunhee Yi et al.

Summary: Oncogenic ecDNA plays a crucial role in tumor evolution, but our understanding of its biology is limited. In this study, we investigated the distribution and frequency of ecDNA copy number in patient tissues and cell line models. We discovered uneven segregation of ecDNA during mitosis and the formation of ecDNA hubs that drive oncogene transcription.

CANCER DISCOVERY (2022)

Article Multidisciplinary Sciences

Chromothripsis drives the evolution of gene amplification in cancer

Ofer Shoshani et al.

Summary: The study reveals that chromothripsis is a major driver of circular extrachromosomal DNA (ecDNA) amplification, mediated by poly(ADP-ribose) polymerases (PARP) and DNA-dependent protein kinase (DNA-PKcs). The structural evolution of ecDNAs further increases drug tolerance, leading to rapid acquisition of tolerance to altered growth conditions. This mechanism accelerates genomic DNA rearrangement and amplification into ecDNA, contributing to cancer therapy resistance.

NATURE (2021)

Editorial Material Oncology

Cancer Grand challenges: Embarking on a New Era of Discovery

Iain Foulkes et al.

Summary: Cancer Grand Challenges is a funding platform that encourages global, multidisciplinary teams of researchers to work together and tackle some of the toughest challenges in cancer research.

CANCER DISCOVERY (2021)

Article Multidisciplinary Sciences

ecDNA hubs drive cooperative intermolecular oncogene expression

King L. Hung et al.

Summary: Extrachromosomal DNA (ecDNA) hubs are clusters of ecDNAs within the nucleus that enable intermolecular enhancer-gene interactions, promoting oncogene overexpression. The protein-tethered ecDNA hubs facilitate intermolecular transcriptional regulation, serving as units of oncogene function and potential targets for cancer therapy.

NATURE (2021)

Article Multidisciplinary Sciences

eccDNAs are apoptotic products with high innate immunostimulatory activity

Yuangao Wang et al.

Summary: By developing a new eccDNA purification and profiling method, the study revealed close-to-random genomic origination, mechanism of biogenesis and function of eccDNAs.

NATURE (2021)

Article Biochemistry & Molecular Biology

MicroDNA levels are dependent on MMEJ, repressed by c-NHEJ pathway, and stimulated by DNA damage

Teressa Paulsen et al.

Summary: This study suggests that microDNA levels are influenced by resection after double-strand DNA break (DSB) and repair by Microhomology Mediated End Joining (MMEJ). The accumulation of microDNA occurs during DNA repair pathways following endogenous or induced DNA breaks.

NUCLEIC ACIDS RESEARCH (2021)

Article Oncology

Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription

Yanfen Zhu et al.

Summary: The study reveals that extrachromosomal, circular DNA (ecDNA) is a common and oncogenic alteration in cancer genomes, impacting transcriptional programs through chromatin interactions. ecDNAs in neurosphere and prostate cancer cell cultures show widespread intra-ecDNA and genome-wide chromosomal interactions, potentially leading to high-level expression of chromosomal genes.

CANCER CELL (2021)

Editorial Material Biochemistry & Molecular Biology

ecDNA party bus: Bringing the enhancer to you

Karen Adelman et al.

Summary: Recent research by Zhu et al. (2021) highlights that extrachromosomal DNA circles containing enhancers can act as mobile regulatory elements, interacting with chromosomal oncogenes to stimulate high-level gene activity, ultimately contributing to tumor heterogeneity and cancer progression.

MOLECULAR CELL (2021)

Article Oncology

Extrachromosomal DNA in HPV-Mediated Oropharyngeal Cancer Drives Diverse Oncogene Transcription

John Pang et al.

Summary: The study revealed that circular oncogenic DNA is a dominant feature in HPVOPC, with a significant portion containing human and human-viral hybrid ecDNA. The expression of these ecDNA has a specific viral oncogene expression pattern that plays a crucial role in driving oncogenic transformation and immune evasion.

CLINICAL CANCER RESEARCH (2021)

Article Biotechnology & Applied Microbiology

GRIDSS2: comprehensive characterisation of somatic structural variation using single breakend variants and structural variant phasing

Daniel L. Cameron et al.

Summary: GRIDSS2 is the first structural variant caller that explicitly reports single breakends breakpoints where only one side can be unambiguously determined. It can explain somatic centromere copy number changes using single breakends to non-centromere sequence.GRIDSS2 achieves a low false negative rate and false discovery rate in metastatic cancers, also identifying a novel duplication signature.

GENOME BIOLOGY (2021)

Article Computer Science, Artificial Intelligence

FaNDOM: Fast nested distance-based seeding of optical maps

Siavash Raeisi Dehkordi et al.

Summary: Optical mapping provides single-molecule readouts of DNA sequence motifs and can be aligned to reference genomes to identify structural variants. FaNDOM is a tool that significantly reduces the search space of alignment, enabling fast and accurate mapping of biologically interesting structural variants.

PATTERNS (2021)

Review Cell Biology

PARP and PARG inhibitors in cancer treatment

Dea Slade

GENES & DEVELOPMENT (2020)

Article Genetics & Heredity

Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma

Richard P. Koche et al.

NATURE GENETICS (2020)

Article Multidisciplinary Sciences

Mechanisms generating cancer genome complexity from a single cell division error

Neil T. Umbreit et al.

SCIENCE (2020)

Article Multidisciplinary Sciences

Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma

Konstantin Helmsauer et al.

NATURE COMMUNICATIONS (2020)

Article Clinical Neurology

Structure and evolution of double minutes in diagnosis and relapse brain tumors

Ke Xu et al.

ACTA NEUROPATHOLOGICA (2019)

Review Cell Biology

Interchromosomal interactions: A genomic love story of kissing chromosomes

Philipp G. Maass et al.

JOURNAL OF CELL BIOLOGY (2019)

Article Biochemistry & Molecular Biology

Functional Enhancers Shape Extrachromosomal Oncogene Amplifications

Andrew R. Morton et al.

Article Multidisciplinary Sciences

Circular ecDNA promotes accessible chromatin and high oncogene expression

Sihan Wu et al.

NATURE (2019)

Article Multidisciplinary Sciences

Exploring the landscape of focal amplifications in cancer using AmpliconArchitect

Viraj Deshpande et al.

NATURE COMMUNICATIONS (2019)

Article Multidisciplinary Sciences

EcSeg: Semantic Segmentation of Metaphase Images Containing Extrachromosomal DNA

Utkrisht Rajkumar et al.

ISCIENCE (2019)

Article Multidisciplinary Sciences

Extrachromosomal circular DNA-based amplification and transmission of herbicide resistance in crop weed Amaranthus palmeri

Dal-Hoe Koo et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

Article Multidisciplinary Sciences

Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity

Kristen M. Turner et al.

NATURE (2017)

Article Biochemical Research Methods

An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues

M. Ryan Corces et al.

NATURE METHODS (2017)

Review Cell Biology

Non-homologous DNA end joining and alternative pathways to double-strand break repair

Howard H. Y. Chang et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2017)

Review Cell Biology

Rebuilding Chromosomes After Catastrophe: Emerging Mechanisms of Chromothripsis

Peter Ly et al.

TRENDS IN CELL BIOLOGY (2017)

Article Multidisciplinary Sciences

Palindromic amplification of the ERBB2 oncogene in primary HER2-positive breast tumors

Michael Marotta et al.

SCIENTIFIC REPORTS (2017)

Article Biochemical Research Methods

OMTools: a software package for visualizing and processing optical mapping data

Alden King-Yung Leung et al.

BIOINFORMATICS (2017)

Article Biochemical Research Methods

ATAC-see reveals the accessible genome by transposase-mediated imaging and sequencing

Xingqi Chen et al.

NATURE METHODS (2016)

Article Multidisciplinary Sciences

Chromothripsis from DNA damage in micronuclei

Cheng-Zhong Zhang et al.

NATURE (2015)

Article Oncology

The Architecture and Evolution of Cancer Neochromosomes

Dale W. Garsed et al.

CANCER CELL (2014)

Article Biochemistry & Molecular Biology

Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability

Keiko Akagi et al.

GENOME RESEARCH (2014)

Article Biochemistry & Molecular Biology

Amplicon rearrangements during the extrachromosomal and intrachromosomal amplification process in a glioma

Nicolas Vogt et al.

NUCLEIC ACIDS RESEARCH (2014)

Article Biochemistry & Molecular Biology

Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer

Alberto L'Abbate et al.

NUCLEIC ACIDS RESEARCH (2014)

Article Multidisciplinary Sciences

Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA

David A. Nathanson et al.

SCIENCE (2014)

Article Biochemistry & Molecular Biology

Diverse Mechanisms of Somatic Structural Variations in Human Cancer Genomes

Lixing Yang et al.

Article Multidisciplinary Sciences

Gemcitabine Eliminates Double Minute Chromosomes from Human Ovarian Cancer Cells

Lisa Yu et al.

PLOS ONE (2013)

Article Multidisciplinary Sciences

An algorithmic approach for breakage-fusion-bridge detection in tumor genomes

Shay Zakov et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

Article Biochemistry & Molecular Biology

A genome-wide analysis of common fragile sites: What features determine chromosomal instability in the human genome?

Arkarachai Fungtammasan et al.

GENOME RESEARCH (2012)

Article Biotechnology & Applied Microbiology

Genome mapping on nanochannel arrays for structural variation analysis and sequence assembly

Ernest T. Lam et al.

NATURE BIOTECHNOLOGY (2012)

Article Biochemistry & Molecular Biology

Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development

Philip J. Stephens et al.

Article Biotechnology & Applied Microbiology

Frequency of double minute chromosomes and combined cytogenetic abnormalities and their characteristics

Yihui Fan et al.

JOURNAL OF APPLIED GENETICS (2011)

Article Biochemistry & Molecular Biology

Gene amplification as double minutes or homogeneously staining regions in solid tumors: Origin and structure

Clelia Tiziana Storlazzi et al.

GENOME RESEARCH (2010)

Article Biochemical Research Methods

Fast and accurate short read alignment with Burrows-Wheeler transform

Heng Li et al.

BIOINFORMATICS (2009)

Article Genetics & Heredity

Have double minutes functioning centromeres?

ALBERT LEVAN et al.

HEREDITAS (2009)

Review Genetics & Heredity

Neocentromeres: New insights into centromere structure, disease development, and karyotype evolution

Owen J. Marshall et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2008)

Article Genetics & Heredity

Fine-scale structural variation of the human genome

E Tuzun et al.

NATURE GENETICS (2005)

Article Multidisciplinary Sciences

Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival

HY Chang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2005)

Article Multidisciplinary Sciences

Molecular structure of double-minute chromosomes bearing amplified copies of the epidermal growth factor receptor gene in gliomas

N Vogt et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2004)

Review Multidisciplinary Sciences

The sequence of the human genome

JC Venter et al.

SCIENCE (2001)

Review Multidisciplinary Sciences

Initial sequencing and analysis of the human genome

ES Lander et al.

NATURE (2001)