Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics.

Abstract:

:Many cancers have substantial genomic heterogeneity within a given tumor, and to fully understand that diversity requires the ability to perform single cell analysis. We performed targeted sequencing of a panel of single nucleotide variants (SNVs), deletions, and IgH sequences in 1,479 single tumor cells from six acute lymphoblastic leukemia (ALL) patients. By accurately segregating groups of cooccurring mutations into distinct clonal populations, we identified codominant clones in the majority of patients. Evaluation of intraclonal mutation patterns identified clone-specific punctuated cytosine mutagenesis events, showed that most structural variants are acquired before SNVs, determined that KRAS mutations occur late in disease development but are not sufficient for clonal dominance, and identified clones within the same patient that are arrested at varied stages in B-cell development. Taken together, these data order the sequence of genetic events that underlie childhood ALL and provide a framework for understanding the development of the disease at single-cell resolution.

authors

Gawad C,Koh W,Quake SR

doi

10.1073/pnas.1420822111

subject

Has Abstract

pub_date

2014-12-16 00:00:00

pages

17947-52

issue

50

eissn

0027-8424

issn

1091-6490

pii

1420822111

journal_volume

111

pub_type

杂志文章
  • Macronuclear DNA of the hypotrichous ciliate Oxytricha fallax.

    abstract::DNA in the macronuclei of Oxytricha fallax, as in other hypotrichous ciliate protozoa, exists as small, achromosomal molecules rather than in chromosomes. We report studies on O. fallax DNA using physicochemical procedures and nucleic acid hybridization. Macronuclear DNA molecules range in size from 22 kilobase pairs ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.10.4992

    authors: Rae PM,Spear BB

    更新日期:1978-10-01 00:00:00

  • Memory stabilization with targeted reactivation during human slow-wave sleep.

    abstract::It is believed that neural representations of recent experiences become reactivated during sleep, and that this process serves to stabilize associated memories in long-term memory. Here, we initiated this reactivation process for specific memories during slow-wave sleep. Participants studied 50 object-location associa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1201072109

    authors: van Dongen EV,Takashima A,Barth M,Zapp J,Schad LR,Paller KA,Fernández G

    更新日期:2012-06-26 00:00:00

  • Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion.

    abstract::Functional lysosomes mediate autophagy and macropinocytosis for nutrient acquisition. Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit high basal lysosomal activity, and inhibition of lysosome function suppresses PDAC cell proliferation and tumor growth. However, the codependencies induced by lysosomal inhibitio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1812410116

    authors: Elliott IA,Dann AM,Xu S,Kim SS,Abt ER,Kim W,Poddar S,Moore A,Zhou L,Williams JL,Capri JR,Ghukasyan R,Matsumura C,Tucker DA,Armstrong WR,Cabebe AE,Wu N,Li L,Le TM,Radu CG,Donahue TR

    更新日期:2019-04-02 00:00:00

  • Anatomy of herpes simplex virus DNA: evidence for four populations of molecules that differ in the relative orientations of their long and short components.

    abstract::Intact DNA molecules extracted from HSV-1 (herpes simplex virus 1, human herpes virus 1) strain MP virions have a molecular weight of approximately 97 X 10(6), but cleavage with the HinIII restriction enzyme yields fourteen fragments with summed molecular weights of 160 X 10(6). Six "major" fragments occur once in eve...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.11.4243

    authors: Hayward GS,Jacob RJ,Wadsworth SC,Roizman B

    更新日期:1975-11-01 00:00:00

  • DNA replication origins in the Schizosaccharomyces pombe genome.

    abstract::Origins of DNA replication in Schizosaccharomyces pombe lack a specific consensus sequence analogous to the Saccharomyces cerevisiae autonomously replicating sequence (ARS) consensus, raising the question of how they are recognized by the replication machinery. Because all well characterized S. pombe origins are locat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0408811102

    authors: Dai J,Chuang RY,Kelly TJ

    更新日期:2005-01-11 00:00:00

  • Generation of fibrosarcomas in vivo by a retrovirus that expresses the normal B chain of platelet-derived growth factor and mimics the alternative splice pattern of the v-sis oncogene.

    abstract::A retrovirus containing the entire human platelet-derived growth factor B-chain (PDGF-B) gene was constructed in order to investigate the in vivo biological activity of its encoded growth factor. When this virus was introduced into newborn mice, it reproducibly generated fibrosarcomas at the site of inoculation. Provi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.8.2693

    authors: Pech M,Gazit A,Arnstein P,Aaronson SA

    更新日期:1989-04-01 00:00:00

  • Quantifying the driving factors for language shift in a bilingual region.

    abstract::Many of the world's around 6,000 languages are in danger of disappearing as people give up use of a minority language in favor of the majority language in a process called language shift. Language shift can be monitored on a large scale through the use of mathematical models by way of differential equations, for examp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.1617252114

    authors: Prochazka K,Vogl G

    更新日期:2017-04-25 00:00:00

  • NG-methyl-L-arginine causes endothelium-dependent contraction and inhibition of cyclic GMP formation in artery and vein.

    abstract::The objective of this study was to determine whether the vascular smooth muscle contractile effect of NG-methyl-L-arginine (NMA) is endothelium dependent and attributed to a decline in smooth muscle levels of cyclic GMP. Vascular smooth muscle levels of cyclic GMP are severalfold greater in endothelium-intact than in ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.12.4430

    authors: Gold ME,Wood KS,Byrns RE,Fukuto J,Ignarro LJ

    更新日期:1990-06-01 00:00:00

  • Endothelial plasmalemmal vesicles as elements in a system of branching invaginations from the cell surface.

    abstract::In electron microscopy studies of the endothelial vesicles in frog mesenteric capillaries, an accidental observation was made concerning vesicular organization. When tannic acid was added to already fixed tissue, the mordant reached apparently free vesicles in the cytoplasm under conditions in which vesicular movement...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.12.6439

    authors: Bundgaard M,Frøkjaer-Jensen J,Crone C

    更新日期:1979-12-01 00:00:00

  • Endoplasmic reticulum localization of the low density lipoprotein receptor mediates presecretory degradation of apolipoprotein B.

    abstract::Mutations in the low density lipoprotein (LDL) receptor (LDLR) cause hypercholesterolemia because of inefficient LDL clearance from the circulation. In addition, there is a paradoxical oversecretion of the metabolic precursor of LDL, very low density lipoprotein (VLDL). We recently demonstrated that the LDLR mediates ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.072557199

    authors: Gillian-Daniel DL,Bates PW,Tebon A,Attie AD

    更新日期:2002-04-02 00:00:00

  • Elevated mutagenesis and decreased DNA repair at a transgene are associated with proliferation but not apoptosis in p53-deficient cells.

    abstract::p53, the most commonly mutated gene in human tumors, is believed to play a crucial role in the prevention of cancer by protecting cells from mutation, a theory commonly known as the "Guardian of the Genome" hypothesis. There are two hypotheses as to how this can occur. In the first, p53 protects the genome by retardin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2235595100

    authors: Bielas JH,Heddle JA

    更新日期:2003-10-28 00:00:00

  • Expressional potency of mRNAs encoding receptors and voltage-activated channels in the postmortem rat brain.

    abstract::The stability and integrity of mRNAs encoding neurotransmitter receptors and voltage-activated channels in the postmortem rat brain was investigated by isolating poly(A)+ mRNA, injecting it into Xenopus oocytes, and then examining the expression of functional neurotransmitter receptors and voltage-activated channels i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.5.1854

    authors: Ragsdale DS,Miledi R

    更新日期:1991-03-01 00:00:00

  • Neuroimaging analyses of human working memory.

    abstract::We review a program of research that uses neuroimaging techniques to determine the functional and neural architecture of human working memory. A first set of studies indicates that verbal working memory includes a storage component, which is implemented neurally by areas in the left-hemisphere posterior parietal corte...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.95.20.12061

    authors: Smith EE,Jonides J

    更新日期:1998-09-29 00:00:00

  • Autophagy-mediated reentry of Francisella tularensis into the endocytic compartment after cytoplasmic replication.

    abstract::Intracellular bacterial pathogens evade the bactericidal functions of mammalian cells by physical escape from their phagosome and replication into the cytoplasm or through the modulation of phagosome maturation and biogenesis of a membrane-bound replicative organelle. Here, we detail in murine primary macrophages the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0601838103

    authors: Checroun C,Wehrly TD,Fischer ER,Hayes SF,Celli J

    更新日期:2006-09-26 00:00:00

  • Reconstruction of the dynamics of the climatic system from time-series data.

    abstract::The oxygen isotope record of the last million years, as provided by a deep sea core sediment, is analyzed by a method recently developed in the theory of dynamical systems. The analysis suggests that climatic variability is the manifestation of a chaotic dynamics described by an attractor of fractal dimensionality. A ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.3.536

    authors: Nicolis C,Nicolis G

    更新日期:1986-02-01 00:00:00

  • Bidirectional control of the chicken beta- and epsilon-globin genes by a shared enhancer.

    abstract::An enhancer specific to erythroid cells was identified previously in the 3' flanking sequence of the chicken adult beta-globin gene and shown to act on the beta-globin promoter. This enhancer lies between the adult beta-globin gene and the embryonic epsilon-globin gene, about equidistant from the two promoters. To det...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.8.2548

    authors: Nickol JM,Felsenfeld G

    更新日期:1988-04-01 00:00:00

  • Differential effects of perhydrohistrionicotoxin on neurally and iontophoretically evoked endplate currents.

    abstract::Perhydrohistrionicotoxin, at concentrations of 10(-12)-10(-7) M, depressed the current generated by iontophoretic application of acetylcholine to endplate regions of soleus and extensor digitorum longus muscles of rats. However, no changes in the amplitude or time course of spontaneous miniature endplate potentials or...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.3.1596

    authors: Albuquerque EX,Gage PW

    更新日期:1978-03-01 00:00:00

  • Natural language indicators of differential gene regulation in the human immune system.

    abstract::Adverse social conditions have been linked to a conserved transcriptional response to adversity (CTRA) in circulating leukocytes that may contribute to social gradients in disease. However, the CNS mechanisms involved remain obscure, in part because CTRA gene-expression profiles often track external social-environment...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1707373114

    authors: Mehl MR,Raison CL,Pace TWW,Arevalo JMG,Cole SW

    更新日期:2017-11-21 00:00:00

  • Reovirus-induced modification of cap-dependent translation in infected L cells.

    abstract::The translational apparatus in cell-free extracts prepared from L cells infected with reovirus undergoes a time-dependent transition from cap dependence to cap independence. Extracts from uninfected L cells translate capped reovirus mRNA at high efficiency and synthesize the expected three size classes of reovirus pol...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.1.152

    authors: Skup D,Millward S

    更新日期:1980-01-01 00:00:00

  • Error rates for nanopore discrimination among cytosine, methylcytosine, and hydroxymethylcytosine along individual DNA strands.

    abstract::Cytosine, 5-methylcytosine, and 5-hydroxymethylcytosine were identified during translocation of single DNA template strands through a modified Mycobacterium smegmatis porin A (M2MspA) nanopore under control of phi29 DNA polymerase. This identification was based on three consecutive ionic current states that correspond...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1310615110

    authors: Schreiber J,Wescoe ZL,Abu-Shumays R,Vivian JT,Baatar B,Karplus K,Akeson M

    更新日期:2013-11-19 00:00:00

  • ERK regulation of phosphodiesterase 4 enhances dopamine-stimulated AMPA receptor membrane insertion.

    abstract::AMPA-type glutamate receptor (AMPAR) trafficking is essential for modulating synaptic transmission strength. Prior studies that have characterized signaling pathways underlying AMPAR trafficking have identified the cAMP/PKA-mediated phosphorylation of GluA1, an AMPAR subunit, as a key step in the membrane insertion of...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1311783110

    authors: Song RS,Massenburg B,Wenderski W,Jayaraman V,Thompson L,Neves SR

    更新日期:2013-09-17 00:00:00

  • Transcription regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators.

    abstract::The structurally diverse peroxisome proliferators ciprofibrate, clofibrate, and bis(2-ethylhexyl) phthalate [(EtHx)2 greater than Pht] increase the activities of hepatic catalase and peroxisomal fatty acid beta-oxidation enzymes in conjunction with profound proliferation of peroxisomes in hepatocytes. In order to deli...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.6.1747

    authors: Reddy JK,Goel SK,Nemali MR,Carrino JJ,Laffler TG,Reddy MK,Sperbeck SJ,Osumi T,Hashimoto T,Lalwani ND

    更新日期:1986-03-01 00:00:00

  • Epstein-Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation.

    abstract::The gene encoding latent-infection membrane protein 1 (LMP1) was specifically mutated in Epstein-Barr virus (EBV) recombinants by inserting a nonsense linker after codon 9 or codon 84 or into an intron 186 bp 3' to the latter insertion site. EBV recombinants with the LMP1 intron mutation were wild type for LMP1 expres...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.19.9150

    authors: Kaye KM,Izumi KM,Kieff E

    更新日期:1993-10-01 00:00:00

  • On the strength of glasses.

    abstract::The remarkable strength of glasses is examined using the random first order transition theory of the glass transition. The theory predicts that strength depends on elastic modulus but also on the configurational energy frozen in when the glass is prepared. The stress catalysis of cooperative rearrangements of the type...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1214130109

    authors: Wisitsorasak A,Wolynes PG

    更新日期:2012-10-02 00:00:00

  • Modeling nuclear volume isotope effects in crystals.

    abstract::Mass-independent isotope fractionations driven by differences in volumes and shapes of nuclei (the field shift effect) are known in several elements and are likely to be found in more. All-electron relativistic electronic structure calculations can predict this effect but at present are computationally intensive and l...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1216216110

    authors: Schauble EA

    更新日期:2013-10-29 00:00:00

  • Duplex DNA catalyzes the chemical rearrangement of a malondialdehyde deoxyguanosine adduct.

    abstract::The primary DNA lesion induced by malondialdehyde, a byproduct of lipid peroxidation and prostaglandin synthesis, is 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)-pyrimido[1, 2-a]purin-10(3H)-one (M1G). When placed opposite cytosine (underlined) at neutral pH in either the d(GGTMTCCG).d(CGGACACC) or d(ATCGCMCGGCATG). d(C...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.12.6615

    authors: Mao H,Schnetz-Boutaud NC,Weisenseel JP,Marnett LJ,Stone MP

    更新日期:1999-06-08 00:00:00

  • Punctuation and syntax of the RNA polymerase II CTD code in fission yeast.

    abstract::The primary structure and phosphorylation pattern of the tandem Y(1)S(2)P(3)T(4)S(5)P(6)S(7) repeats of the RNA polymerase II carboxyl-terminal domain (CTD) convey information about the transcription apparatus--a CTD code--to a large ensemble of CTD-binding receptor proteins. Four of the seven coding "letters" of the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1208995109

    authors: Schwer B,Sanchez AM,Shuman S

    更新日期:2012-10-30 00:00:00

  • Effects of in vivo adventitial expression of recombinant endothelial nitric oxide synthase gene in cerebral arteries.

    abstract::Nitric oxide (NO), synthesized from L-arginine by NO synthases (NOS), plays an essential role in the regulation of cerebrovascular tone. Adenoviral vectors have been widely used to transfer recombinant genes to different vascular beds. To determine whether the recombinant endothelial NOS (eNOS) gene can be delivered i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.23.12568

    authors: Chen AF,Jiang SW,Crotty TB,Tsutsui M,Smith LA,O'Brien T,Katusic ZS

    更新日期:1997-11-11 00:00:00

  • Sequence physical properties encode the global organization of protein structure space.

    abstract::It is demonstrated that, properly represented, the amino acid composition of protein sequences contains the information necessary to delineate the global properties of protein structure space. A numerical representation of amino acid sequence in terms of a set of property factors is used, and the values of those prope...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0903433106

    authors: Rackovsky S

    更新日期:2009-08-25 00:00:00

  • The karrikin signaling regulator SMAX1 controls Lotus japonicus root and root hair development by suppressing ethylene biosynthesis.

    abstract::An evolutionarily ancient plant hormone receptor complex comprising the α/β-fold hydrolase receptor KARRIKIN INSENSITIVE 2 (KAI2) and the F-box protein MORE AXILLARY GROWTH 2 (MAX2) mediates a range of developmental responses to smoke-derived butenolides called karrikins (KARs) and to yet elusive endogenous KAI2 ligan...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2006111117

    authors: Carbonnel S,Das D,Varshney K,Kolodziej MC,Villaécija-Aguilar JA,Gutjahr C

    更新日期:2020-09-01 00:00:00