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| Open AccessMutation rate plasticity in rifampicin resistance depends on Escherichia coli cell–cell interactions
The factors varying mutation rate at a particular site in a single genotype remain elusive. Here, Krašovec et al. show that mutation rates at sites conferring resistance to rifampicin in Escherichia coli decrease with population density, and that mutation-rate plasticity is controlled by the luxSgene.
- Rok Krašovec
- , Roman V. Belavkin
- & Christopher G. Knight
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Article
| Open AccessMaternal nutrition at conception modulates DNA methylation of human metastable epialleles
Maternal diet affects DNA methylation in the developing offspring, leading to phenotypic changes. Here, Dominguez-Salas et al. exploit seasonal variation in the diet of Gambian women to show that maternal methyl donor nutrient status around the time of conception predicts methylation levels at metastable epialleles in infants.
- Paula Dominguez-Salas
- , Sophie E. Moore
- & Branwen J. Hennig
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Chromatin retention of DNA damage sensors DDB2 and XPC through loss of p97 segregase causes genotoxicity
Nucleotide excision repair protects the genome from UV light-induced damage. Here, Puumalainen et al. show that chromatin retention of the UV lesion sensors DDB2 and XPC due to a lack of p97 segregase impairs excision repair, revealing that DNA lesion-associated protein homeostasis affects genome stability.
- Marjo-Riitta Puumalainen
- , Davor Lessel
- & Hanspeter Naegeli
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Targeted genomic rearrangements using CRISPR/Cas technology
Genomic rearrangements have important functional consequences for cancer. Here, Choi and Meyerson use CRISPR/Cas technology to generate translocations and inversions that are known drivers of lung cancer, and demonstrate the utility of this technology for studying the role of genomic rearrangements in disease.
- Peter S. Choi
- & Matthew Meyerson
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Article
| Open AccessThe emerging biofuel crop Camelina sativa retains a highly undifferentiated hexaploid genome structure
Camelina sativa is an oilseed crop with important industrial applications. Here, the authors sequence the C. sativagenome to investigate the genome organization and evolution of this species, and to provide a valuable tool for genetic engineering and potential crop improvement.
- Sateesh Kagale
- , Chushin Koh
- & Isobel A. P. Parkin
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Article
| Open AccessThe rainbow trout genome provides novel insights into evolution after whole-genome duplication in vertebrates
Although whole-genome duplications (WGDs) are rare events, they have an important role in shaping vertebrate evolution. Here, the authors sequence the rainbow trout genome and show that rediploidization after WGD occurs in a slow and stepwise manner.
- Camille Berthelot
- , Frédéric Brunet
- & Yann Guiguen
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Article |
Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development
Alternative splicing is a process during gene expression that increases the diversity of proteins encoded by a single gene. Here, the authors perform RNA-sequencing on cardiac cells from mice and show that extensive changes in gene expression and alternative splicing occur during the first month after birth.
- Jimena Giudice
- , Zheng Xia
- & Thomas A. Cooper
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Article
| Open AccessVariation in Arabidopsis flowering time associated with cis-regulatory variation in CONSTANS
The transcription factor CONSTANS regulates the timing of flowering in Arabidopsis. Rosas et al. report that genetic variation in the cis-regulatory regions of this gene contributes to natural phenotypic variation in flowering time.
- Ulises Rosas
- , Yu Mei
- & Michael D. Purugganan
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Forensic genomics as a novel tool for identifying the causes of mass mortality events
Mass mortality events of fish and invertebrates are increasingly frequent in coastal zones, yet it is often difficult to identify their causes. Here, the authors provide evidence that a combined field and genomics approach could help identifying the specific cause of mass mortality events.
- Pierre De Wit
- , Laura Rogers-Bennett
- & Stephen R. Palumbi
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Article
| Open AccessNovel skin phenotypes revealed by a genome-wide mouse reverse genetic screen
Large-scale efforts are put into the generation of knockout mutant mice for many individual genes. Here, the authors systematically screen skin from 538 mutant mice and identify 50 mutants with epidermal phenotypes, of which 9 are also associated with human skin defects.
- Kifayathullah Liakath-Ali
- , Valerie E. Vancollie
- & Fiona M. Watt
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Article
| Open AccessProtein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism
Autism spectrum disorder (ASD) is a complex genetic trait that encompasses a range of neurodevelopmental disorders. Here, the authors clone brain-expressed alternatively-spliced isoforms of ASD risk factors and construct a network of protein interactions that provides further insight into the disease aetiology.
- Roser Corominas
- , Xinping Yang
- & Lilia M. Iakoucheva
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A mutation in the enzyme monoamine oxidase explains part of the Astyanax cavefish behavioural syndrome
Astyanax mexicanus exists as either river-dwelling or cave-adapted subtypes. Elipot et al.identify a mutation in the cavefish monoamine oxidase gene, which leads to differential serotonin degradation in the brain and which may be associated with differences in behaviour between the subtypes.
- Yannick Elipot
- , Hélène Hinaux
- & Sylvie Rétaux
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Article
| Open AccessImpact of genomic polymorphisms on the repertoire of human MHC class I-associated peptides
Mass spectrometry (MS) has furthered our understanding of MHC class I-associated peptides (MIPs), but the technique is inadequate for studying MIP-associated polymorphisms. Here, the authors combine high-throughput MS with exome and transcriptome sequencing to identify polymorphic MIPs from two female siblings.
- Diana Paola Granados
- , Dev Sriranganadane
- & Claude Perreault
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The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes
Proteins involved in epigenetic regulation are frequently mutated in several paediatric cancers. Here, Huether et al.characterize the somatic mutation frequency across 21 paediatric cancer subtypes by sequencing 633 epigenetic genes in over 1,000 tumours; generating a rich data set for investigating epigenetic dysregulation.
- Robert Huether
- , Li Dong
- & James R. Downing
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PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system
Epigenetic codes translate external stimuli into targeted and long-lasting gene regulation. In this study, the authors show that regenerative retrograde signalling activates the epigenetic modifying enzyme PCAF, inducing gene expression and promoting axon regeneration in a mouse spinal cord injury model.
- Radhika Puttagunta
- , Andrea Tedeschi
- & Simone Di Giovanni
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Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids
Pulmonary carcinoids account for about 2% of pulmonary neoplasms. Here, the authors carry out gene copy number analysis, genome/exome, and transcriptome sequencing of pulmonary carcinoids and identify frequent mutations in chromatin-remodelling genes that can drive tumorigenesis in these tumours.
- Lynnette Fernandez-Cuesta
- , Martin Peifer
- & Roman K. Thomas
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Mutations in epigenetic regulators including SETD2 are gained during relapse in paediatric acute lymphoblastic leukaemia
Epigenetic regulators have been proposed to be modulators of chemoresistance in acute lymphoblastic leukaemia. Here, the authors find enrichment of mutations in epigenetic regulators at relapse, including somatic mutations in SETD2.
- Brenton G. Mar
- , Lars B. Bullinger
- & Scott A. Armstrong
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A genetic and computational approach to structurally classify neuronal types
Cell type classification is commonly used to interpret the connectivity and functional output of neuronal networks. Here, Sümbül et al. combine structural and genetic approaches to provide a higher resolution classification of neuronal subtypes.
- Uygar Sümbül
- , Sen Song
- & H. Sebastian Seung
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Article |
Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance
Superoxide dismutase 1 protects cells from reactive oxygen species by catalysing the conversion of superoxide into hydrogen peroxide. Tsang et al.show that this enzyme also plays a transcriptional role in the nucleus, regulating antioxidant gene expression in response to oxidative stress signalling.
- Chi Kwan Tsang
- , Yuan Liu
- & X. F. S. Zheng
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Evolution under monogamy feminizes gene expression in Drosophila melanogaster
Males and females show unique patterns of gene expression, but it is unclear if this dimorphism is genetically constrained. Here, Hollis et al. use experimental evolution in Drosophila melanogasterto reveal unresolved conflict between the sexes over gene expression caused by sexual selection.
- Brian Hollis
- , David Houle
- & Laurent Keller
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Non-canonical function of spindle assembly checkpoint proteins after APC activation reduces aneuploidy in mouse oocytes
The spindle assembly checkpoint (SAC) has been viewed as a switch that prevents chromosome segregation until all chromosomes are correctly attached to spindle microtubules. Lane and Jones show that in meiosis I, SAC proteins remain partially active after prometaphase, and prevent aneuploidy by prolonging meiosis.
- Simon I.R. Lane
- & Keith T. Jones
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Article
| Open AccessMetabolome-based genome-wide association study of maize kernel leads to novel biochemical insights
Plants produce a variety of metabolites that have a critical role in growth and development. Here, the authors carry out a genome-wide association analysis of metabolites and metabolite features in maize and identify candidate genes involved in secondary metabolism, and a potential biomarker for the genetic improvement of the crop.
- Weiwei Wen
- , Dong Li
- & Jianbing Yan
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Article |
Genome-wide association study reveals two new risk loci for bipolar disorder
Bipolar disorder (BD) is a severe mood disorder, which has been shown to have a large genetic component. Here the authors identify two previously unreported BD risk loci and provide further insights into the biological mechanisms underlying BD development.
- Thomas W. Mühleisen
- , Markus Leber
- & Sven Cichon
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Article |
Mutations in Alström protein impair terminal differentiation of cardiomyocytes
Cardiomyocyte cell cycle arrest is important for mammalian heart maturation, but the process is poorly understood. Here, the authors use exome sequencing to identify compound heterozygous ALMS1mutations associated with cardiomyocyte replication and provide evidence that Alström protein deficiency impairs postnatal cardiomyocyte cell cycle arrest.
- Lincoln T. Shenje
- , Peter Andersen
- & Daniel P. Judge
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Article |
HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells
Lipoproteins such as HDL can bind and transport microRNAs throughout the body. Here the authors provide a new mechanism contributing to the anti-inflammatory effects of HDL by which HDL-associated miR-223 is transferred to endothelial cells, where it inhibits expression of the adhesion molecule ICAM-1.
- Fatiha Tabet
- , Kasey C. Vickers
- & Kerry-Anne Rye
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Characterizing the genetic basis of methylome diversity in histologically normal human lung tissue
The effects of genetic variation on DNA methylation patterns are poorly understood. Here, Shi et al.systematically map methylation-quantitative trait loci in lung, breast and kidney tissue to reveal the impact of inherited variation on the human methylome, which also affects cancer risk.
- Jianxin Shi
- , Crystal N. Marconett
- & Maria Teresa Landi
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Article |
Telomerase reverse transcriptase promoter mutations in primary cutaneous melanoma
Cutaneous melanoma is an aggressive form of skin cancer. Here, the authors show that mutations in the TERT promoter of 287 primary melanomas are associated with age, Breslow thickness and tumour ulceration and frequently occur at sun-exposed sites.
- Barbara Heidenreich
- , Eduardo Nagore
- & Rajiv Kumar
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Article
| Open AccessThe origin of the bifurcated axial skeletal system in the twin-tail goldfish
The ornamental twin-tail goldfish has a bifurcated caudal skeleton that arose during domestication, but the developmental mechanisms that generate this tail are unknown. Here, Abe et al. show that a mutation in the chordingene affects embryonic dorsal–ventral patterning causing the bifurcated tail skeleton.
- Gembu Abe
- , Shu-Hua Lee
- & Kinya G. Ota
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Article |
Epistasis between adults and larvae underlies caste fate and fitness in a clonal ant
It is unclear how interactions between individual genomes affect behaviour and survival in social organisms. Here, Teseo et al. show that genomic interactions between larvae and nursing adults of the clonal ant Cerapachys biroidetermine the proportion of individuals involved in reproduction or cooperation.
- Serafino Teseo
- , Nicolas Châline
- & Daniel J.C. Kronauer
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Article
| Open AccessA two-locus interaction causes interspecific hybrid weakness in rice
Hybrids often show poorer performance than their parents due to conflict between parental genes, but the underlying mechanisms are not well understood. Here, Chen et al. identify three genes that activate immune responses and hinder hybrids growth in rice, a finding that may help rice breeding.
- Chen Chen
- , Hao Chen
- & Hong-Xuan Lin
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Article |
Horizontal gene transfer of a vertebrate vasodilatory hormone into ticks
The impact of horizontal gene transfer (HGT) on the evolution of higher eukaryotes is not fully understood. Here the authors suggest that the vertebrate vasodilator, adrenomedullin (ADM), was horizontally acquired by ticks and hypothesize that the HGT of ADM triggers the emergence of a new tick genus.
- Shiroh Iwanaga
- , Haruhiko Isawa
- & Masao Yuda
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Article
| Open AccessPopulation genomics supports baculoviruses as vectors of horizontal transfer of insect transposons
Horizontal transfer of DNA is common among eukaryotes but the vectors involved remain elusive. Here, Gilbert et al. show high frequency of in vivotransposition from the cabbage looper moth into genomes of a baculovirus, suggesting that viruses can act as vectors of horizontal transfer between animals.
- Clément Gilbert
- , Aurélien Chateigner
- & Richard Cordaux
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Article |
Genome-wide transcriptome profiling of homologous recombination DNA repair
Defects in the homologous recombination repair of DNA can result in gene mutation and cancer. In this study, Peng et al.identify a gene signature associated with homologous recombination repair deficiency and show that this can be used both to predict repair defects and clinical outcome in cancer patients.
- Guang Peng
- , Curtis Chun-Jen Lin
- & Shiaw-Yih Lin
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Article |
Genome-wide RNAi ionomics screen reveals new genes and regulation of human trace element metabolism
The composition of trace elements in human cells (the ionome) is an important component of metabolism. Here, the authors carry out a high-throughput, genome-wide analysis of the human ionome and identify cellular regulators of important trace elements such as selenium, copper and iron.
- Mikalai Malinouski
- , Nesrin M. Hasan
- & Vadim N. Gladyshev
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Article |
Functional analysis of a de novo GRIN2A missense mutation associated with early-onset epileptic encephalopathy
N-methyl-D-aspartate receptors (NMDARs) are key regulators of neuronal excitability in the brain and NMDAR mutations are implicated in epilepsy. Here, the authors identify a NMDAR subunit mutation in a child with epileptic encephalopathy, and show that this mutation increases the activity of NMDAR channels.
- Hongjie Yuan
- , Kasper B. Hansen
- & Stephen F. Traynelis
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A Polymerase Theta-dependent repair pathway suppresses extensive genomic instability at endogenous G4 DNA sites
Genomes contain tracts of tandem guanines, which can adopt stable G-quadruplex structures that obstruct replication fork movement. Here, Koole et al. describe a non-canonical polymerase Theta-dependent repair pathway that prevents genomic instability caused by these replication barriers.
- Wouter Koole
- , Robin van Schendel
- & Marcel Tijsterman
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A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish
The telomerase reverse transcriptase promotes the development of haematopoietic cells in zebrafish independent of its telomere-lengthening activity. Here Alcaraz-Pérez et al.show that the telomerase RNA component regulates cell fate during zebrafish myelopoiesis also in a non-canonical manner.
- Francisca Alcaraz-Pérez
- , Jesús García-Castillo
- & María L. Cayuela
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The impact of agricultural emergence on the genetic history of African rainforest hunter-gatherers and agriculturalists
Agriculture emerged in West Africa 5,000 years ago but how this impacted the population of rainforest hunter-gatherers (RHGs) is unknown. Here, the authors show that modern-day RHG populations present up to 50% of farmer ancestry but admixture only occurred in the last 1,000 years.
- Etienne Patin
- , Katherine J. Siddle
- & Lluís Quintana-Murci
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Tailless and Atrophin control Drosophila aggression by regulating neuropeptide signalling in the pars intercerebralis
It is unclear whether the mechanisms giving rise to aggression in animals are conserved across the animal kingdom. Here, the authors show that knockdown of tailless, an orthologue of a mouse gene involved in aggression, leads to increased aggression in Drosophila, suggesting that the molecular mechanisms behind aggression are conserved.
- Shaun M. Davis
- , Amanda L. Thomas
- & Herman A. Dierick
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Article
| Open AccessDifferential methylation of the TRPA1 promoter in pain sensitivity
Genetically identical twins provide a valuable resource to identify epigenetic factors associated with complex traits. Here the authors adopt this approach and find that differential methylation of the pain gene TRPA1is associated with pain sensitivity in humans.
- J.T. Bell
- , A.K. Loomis
- & T.D. Spector
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Article |
Gene co-expression network analysis reveals common system-level properties of prognostic genes across cancer types
Many studies provide evidence of genes that are associated with cancer prognosis but a global view of these genes is lacking. Using data from ‘The Cancer Genome Atlas’, Yang et al.investigate the network properties of prognostic genes and show that these genes tend to be within highly interconnected groups but not the most connected nodes in the gene co-expression network.
- Yang Yang
- , Leng Han
- & Han Liang
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Article |
Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol
Organisms can adapt to environmental change but how this affects metabolism is unclear. Here, the authors provide a detailed analysis of the effects of individual adaptive mutations on the metabolic network in E. coli, and find evidence of metabolic reprogramming during laboratory evolution on glycerol.
- Kian-Kai Cheng
- , Baek-Seok Lee
- & Martin Robert
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Article |
Dynamic reassortments and genetic heterogeneity of the human-infecting influenza A (H7N9) virus
H7N9 influenza A viruses capable of infecting humans have recently emerged in China. Here, the authors show that these viruses remain genetically diverse, suggesting that they are still in the process of adapting to human hosts.
- Lunbiao Cui
- , Di Liu
- & George F. Gao
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Article |
Integrated analysis of germline and somatic variants in ovarian cancer
Ovarian cancer is one of the most common cancers in women and has an average 5-year survival of only 43%. Here, Kanchi et al.describe the germline and somatic mutation spectrum in ovarian cancer patients and identify potential risk variants associated with the disease.
- Krishna L. Kanchi
- , Kimberly J. Johnson
- & Li Ding
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Article |
Kinase fusions are frequent in Spitz tumours and spitzoid melanomas
Spitzoid neoplasms constitute a spectrum of melanocytic tumours, characterized by distinct clinical, pathological and genetic features. Here, Wiesner et al. show that kinase fusions represent the majority of oncogenic aberrations in spitzoid neoplasms and may serve as therapeutic targets for metastatic spitzoid melanoma.
- Thomas Wiesner
- , Jie He
- & Boris C. Bastian
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Article
| Open AccessDrawing a high-resolution functional map of adeno-associated virus capsid by massively parallel sequencing
Adeno-associated viruses (AAV) are promising gene transfer vectors for human gene therapy. Here, the authors report a high-throughput, sequencing-based method for characterizing amino acid function in AAV capsids and highlight the potential of this method for improving capsid design.
- Kei Adachi
- , Tatsuji Enoki
- & Hiroyuki Nakai
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Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation
The mitochondrial transcription factor TFAM is a multifunctional DNA-binding protein essential for transcriptional regulation and mitochondrial DNA organization. Here, Ngo et al.present two novel crystal structures that provide additional mechanistic insight into how TFAM performs its diverse functions.
- Huu B. Ngo
- , Geoffrey A. Lovely
- & David C. Chan
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Kctd10 regulates heart morphogenesis by repressing the transcriptional activity of Tbx5a in zebrafish
T-box transcription factors such as Tbx5 have essential roles during cardiac development. Here the authors show that a member of the potassium channel tetramerization domain-containing family, Kctd10 is required for zebrafish heart development and represses the transcriptional activity of Tbx5.
- Xiangjun Tong
- , Yao Zu
- & Bo Zhang
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Article
| Open AccessHeterogeneity of genomic evolution and mutational profiles in multiple myeloma
Multiple myeloma is a malignant plasma cell disorder with a complex molecular pathogenesis. Here, the authors perform whole-exome sequencing, copy-number profiling and cytogenetic analysis in 84 myeloma samples and highlight the diversity and evolution of the mutational profile underlying the disease.
- Niccolo Bolli
- , Hervé Avet-Loiseau
- & Nikhil C. Munshi
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