The evolution of relapse of adult T cell acute lymphoblastic leukemia.

Abstract:

BACKGROUND:Adult T cell acute lymphoblastic leukemia (T-ALL) is a rare disease that affects less than 10 individuals in one million. It has been less studied than its cognate pediatric malignancy, which is more prevalent. A higher percentage of the adult patients relapse, compared to children. It is thus essential to study the mechanisms of relapse of adult T-ALL cases. RESULTS:We profile whole-genome somatic mutations of 19 primary T-ALLs from adult patients and the corresponding relapse malignancies and analyze their evolution upon treatment in comparison with 238 pediatric and young adult ALL cases. We compare the mutational processes and driver mutations active in primary and relapse adult T-ALLs with those of pediatric patients. A precise estimation of clock-like mutations in leukemic cells shows that the emergence of the relapse clone occurs several months before the diagnosis of the primary T-ALL. Specifically, through the doubling time of the leukemic population, we find that in at least 14 out of the 19 patients, the population of relapse leukemia present at the moment of diagnosis comprises more than one but fewer than 108 blasts. Using simulations, we show that in all patients the relapse appears to be driven by genetic mutations. CONCLUSIONS:The early appearance of a population of leukemic cells with genetic mechanisms of resistance across adult T-ALL cases constitutes a challenge for treatment. Improving early detection of the malignancy is thus key to prevent its relapse.

journal_name

Genome Biol

journal_title

Genome biology

authors

Sentís I,Gonzalez S,Genescà E,García-Hernández V,Muiños F,Gonzalez C,López-Arribillaga E,Gonzalez J,Fernandez-Ibarrondo L,Mularoni L,Espinosa L,Bellosillo B,Ribera JM,Bigas A,Gonzalez-Perez A,Lopez-Bigas N

doi

10.1186/s13059-020-02192-z

subject

Has Abstract

pub_date

2020-11-23 00:00:00

pages

284

issue

1

eissn

1474-7596

issn

1474-760X

pii

10.1186/s13059-020-02192-z

journal_volume

21

pub_type

杂志文章
  • A simple strategy for heritable chromosomal deletions in zebrafish via the combinatorial action of targeting nucleases.

    abstract::Precise and effective genome-editing tools are essential for functional genomics and gene therapy. Targeting nucleases have been successfully used to edit genomes. However, whole-locus or element-specific deletions abolishing transcript expression have not previously been reported. Here, we show heritable targeting of...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2013-14-7-r69

    authors: Lim S,Wang Y,Yu X,Huang Y,Featherstone MS,Sampath K

    更新日期:2013-07-01 00:00:00

  • The impact of chromatin modifiers on the timing of locus replication in mouse embryonic stem cells.

    abstract:BACKGROUND:The time of locus replication during S-phase is tightly regulated and correlates with chromatin state. Embryonic stem (ES) cells have an unusual chromatin profile where many developmental regulator genes that are not yet expressed are marked by both active and repressive histone modifications. This poised or...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2007-8-8-r169

    authors: Jørgensen HF,Azuara V,Amoils S,Spivakov M,Terry A,Nesterova T,Cobb BS,Ramsahoye B,Merkenschlager M,Fisher AG

    更新日期:2007-01-01 00:00:00

  • Escape from X inactivation in mice and humans.

    abstract::A subset of X-linked genes escapes silencing by X inactivation and is expressed from both X chromosomes in mammalian females. Species-specific differences in the identity of these genes have recently been discovered, suggesting a role in the evolution of sex differences. Chromatin analyses have aimed to discover how g...

    journal_title:Genome biology

    pub_type: 杂志文章,评审

    doi:10.1186/gb-2010-11-6-213

    authors: Berletch JB,Yang F,Disteche CM

    更新日期:2010-01-01 00:00:00

  • The Network of Cancer Genes (NCG): a comprehensive catalogue of known and candidate cancer genes from cancer sequencing screens.

    abstract::The Network of Cancer Genes (NCG) is a manually curated repository of 2372 genes whose somatic modifications have known or predicted cancer driver roles. These genes were collected from 275 publications, including two sources of known cancer genes and 273 cancer sequencing screens of more than 100 cancer types from 34...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-018-1612-0

    authors: Repana D,Nulsen J,Dressler L,Bortolomeazzi M,Venkata SK,Tourna A,Yakovleva A,Palmieri T,Ciccarelli FD

    更新日期:2019-01-03 00:00:00

  • Opening sequence: computational genomics in the era of high-throughput sequencing.

    abstract::A report on the 11th Cold Spring Harbor Laboratory/Wellcome Trust conference on Genome Informatics, Cold Spring Harbor Laboratories, New York, USA, November 2-5, 2011. ...

    journal_title:Genome biology

    pub_type:

    doi:10.1186/gb-2011-12-12-310

    authors: Chambers EV,Kindt AS,Semple CA

    更新日期:2011-12-28 00:00:00

  • FitSNPs: highly differentially expressed genes are more likely to have variants associated with disease.

    abstract:BACKGROUND:Candidate single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWASs) were often selected for validation based on their functional annotation, which was inadequate and biased. We propose to use the more than 200,000 microarray studies in the Gene Expression Omnibus to systematically p...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2008-9-12-r170

    authors: Chen R,Morgan AA,Dudley J,Deshpande T,Li L,Kodama K,Chiang AP,Butte AJ

    更新日期:2008-01-01 00:00:00

  • Capture Hi-C identifies a novel causal gene, IL20RA, in the pan-autoimmune genetic susceptibility region 6q23.

    abstract:BACKGROUND:The identification of causal genes from genome-wide association studies (GWAS) is the next important step for the translation of genetic findings into biologically meaningful mechanisms of disease and potential therapeutic targets. Using novel chromatin interaction detection techniques and allele specific as...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-016-1078-x

    authors: McGovern A,Schoenfelder S,Martin P,Massey J,Duffus K,Plant D,Yarwood A,Pratt AG,Anderson AE,Isaacs JD,Diboll J,Thalayasingam N,Ospelt C,Barton A,Worthington J,Fraser P,Eyre S,Orozco G

    更新日期:2016-11-01 00:00:00

  • RNA methylomes reveal the m6A-mediated regulation of DNA demethylase gene SlDML2 in tomato fruit ripening.

    abstract:BACKGROUND:Methylation of nucleotides, notably in the forms of 5-methylcytosine (5mC) in DNA and N6-methyladenosine (m6A) in mRNA, carries important information for gene regulation. 5mC has been elucidated to participate in the regulation of fruit ripening, whereas the function of m6A in this process and the interplay ...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-019-1771-7

    authors: Zhou L,Tian S,Qin G

    更新日期:2019-08-06 00:00:00

  • Selection in the evolution of gene duplications.

    abstract:BACKGROUND:Gene duplications have a major role in the evolution of new biological functions. Theoretical studies often assume that a duplication per se is selectively neutral and that, following a duplication, one of the gene copies is freed from purifying (stabilizing) selection, which creates the potential for evolut...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2002-3-2-research0008

    authors: Kondrashov FA,Rogozin IB,Wolf YI,Koonin EV

    更新日期:2002-01-01 00:00:00

  • Genomic analysis of the eukaryotic protein kinase superfamily: a perspective.

    abstract::Protein kinases with a conserved catalytic domain make up one of the largest 'superfamilies' of eukaryotic proteins and play many key roles in biology and disease. Efforts to identify and classify all the members of the eukaryotic protein kinase superfamily have recently culminated in the mining of essentially complet...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2003-4-5-111

    authors: Hanks SK

    更新日期:2003-01-01 00:00:00

  • Nucleosome deposition and DNA methylation at coding region boundaries.

    abstract:BACKGROUND:Nucleosome deposition downstream of transcription initiation and DNA methylation in the gene body suggest that control of transcription elongation is a key aspect of epigenetic regulation. RESULTS:Here we report a genome-wide observation of distinct peaks of nucleosomes and methylation at both ends of a pro...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2009-10-9-r89

    authors: Choi JK,Bae JB,Lyu J,Kim TY,Kim YJ

    更新日期:2009-01-01 00:00:00

  • Consistent probabilistic outputs for protein function prediction.

    abstract::In predicting hierarchical protein function annotations, such as terms in the Gene Ontology (GO), the simplest approach makes predictions for each term independently. However, this approach has the unfortunate consequence that the predictor may assign to a single protein a set of terms that are inconsistent with one a...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2008-9-s1-s6

    authors: Obozinski G,Lanckriet G,Grant C,Jordan MI,Noble WS

    更新日期:2008-01-01 00:00:00

  • Decoding dosage compensation.

    abstract::How the mechanisms of dosage compensation distinguish the sex chromosomes from the autosomes has been something of a mystery. A recent study in Caenorhabditis elegans has identified clusters of two common DNA motifs as a cis-acting code for the recruitment of the DCC, the protein complex that mediates dosage compensat...

    journal_title:Genome biology

    pub_type: 杂志文章,评审

    doi:10.1186/gb-2007-8-2-204

    authors: Deng X,Disteche CM

    更新日期:2007-01-01 00:00:00

  • Games with a scientific purpose.

    abstract::The protein folding game Foldit shows that games are an effective way to recruit, engage and organize ordinary citizens to help solve difficult scientific problems. ...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2011-12-12-135

    authors: Good BM,Su AI

    更新日期:2011-12-28 00:00:00

  • In vivo nuclear RNA structurome reveals RNA-structure regulation of mRNA processing in plants.

    abstract:BACKGROUND:mRNA processing is critical for gene expression. A challenge in regulating mRNA processing is how to recognize the actual mRNA processing sites, such as splice and polyadenylation sites, when the sequence content is insufficient for this purpose. Previous studies suggested that RNA structure affects mRNA pro...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-020-02236-4

    authors: Liu Z,Liu Q,Yang X,Zhang Y,Norris M,Chen X,Cheema J,Zhang H,Ding Y

    更新日期:2021-01-04 00:00:00

  • Detection of circular RNA expression and related quantitative trait loci in the human dorsolateral prefrontal cortex.

    abstract:BACKGROUND:Circular RNAs (circRNAs) are implicated in various biological processes. As a layer of the gene regulatory network, circRNA expression is also an intermediate phenotype bridging genetic variation and phenotypic changes. Thus, analyzing circRNA expression variation will shed light on molecular fundamentals of...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-019-1701-8

    authors: Liu Z,Ran Y,Tao C,Li S,Chen J,Yang E

    更新日期:2019-05-20 00:00:00

  • EMu: probabilistic inference of mutational processes and their localization in the cancer genome.

    abstract::The spectrum of mutations discovered in cancer genomes can be explained by the activity of a few elementary mutational processes. We present a novel probabilistic method, EMu, to infer the mutational signatures of these processes from a collection of sequenced tumors. EMu naturally incorporates the tumor-specific oppo...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2013-14-4-r39

    authors: Fischer A,Illingworth CJ,Campbell PJ,Mustonen V

    更新日期:2013-04-29 00:00:00

  • The Adult Mouse Anatomical Dictionary: a tool for annotating and integrating data.

    abstract::We have developed an ontology to provide standardized nomenclature for anatomical terms in the postnatal mouse. The Adult Mouse Anatomical Dictionary is structured as a directed acyclic graph, and is organized hierarchically both spatially and functionally. The ontology will be used to annotate and integrate different...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2005-6-3-r29

    authors: Hayamizu TF,Mangan M,Corradi JP,Kadin JA,Ringwald M

    更新日期:2005-01-01 00:00:00

  • The draft genome of the C3 panicoid grass species Dichanthelium oligosanthes.

    abstract:BACKGROUND:Comparisons between C3 and C4 grasses often utilize C3 species from the subfamilies Ehrhartoideae or Pooideae and C4 species from the subfamily Panicoideae, two clades that diverged over 50 million years ago. The divergence of the C3 panicoid grass Dichanthelium oligosanthes from the independent C4 lineages ...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-016-1080-3

    authors: Studer AJ,Schnable JC,Weissmann S,Kolbe AR,McKain MR,Shao Y,Cousins AB,Kellogg EA,Brutnell TP

    更新日期:2016-10-28 00:00:00

  • Predicting the effects of frameshifting indels.

    abstract::Each human has approximately 50 to 280 frameshifting indels, yet their implications are unknown. We created SIFT Indel, a prediction method for frameshifting indels that has 84% accuracy. The percentage of human frameshifting indels predicted to be gene-damaging is negatively correlated with allele frequency. We also ...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2012-13-2-r9

    authors: Hu J,Ng PC

    更新日期:2012-02-09 00:00:00

  • The Smads.

    abstract:SUMMARY:The large transforming growth factor-beta (TGFbeta) superfamily of secreted proteins regulate the growth, development and differentiation of cells in diverse organisms, including nematode worms, flies, mice and humans. Signals are initiated upon binding of TGFbeta superfamily members to cell-surface serine/thre...

    journal_title:Genome biology

    pub_type: 杂志文章,评审

    doi:10.1186/gb-2001-2-8-reviews3010

    authors: Attisano L,Lee-Hoeflich ST

    更新日期:2001-01-01 00:00:00

  • quantro: a data-driven approach to guide the choice of an appropriate normalization method.

    abstract::Normalization is an essential step in the analysis of high-throughput data. Multi-sample global normalization methods, such as quantile normalization, have been successfully used to remove technical variation. However, these methods rely on the assumption that observed global changes across samples are due to unwanted...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-015-0679-0

    authors: Hicks SC,Irizarry RA

    更新日期:2015-06-04 00:00:00

  • Identifying repeat domains in large genomes.

    abstract::We present a graph-based method for the analysis of repeat families in a repeat library. We build a repeat domain graph that decomposes a repeat library into repeat domains, short subsequences shared by multiple repeat families, and reveals the mosaic structure of repeat families. Our method recovers documented mosaic...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2006-7-1-r7

    authors: Zhi D,Raphael BJ,Price AL,Tang H,Pevzner PA

    更新日期:2006-01-01 00:00:00

  • Genome-wide analysis of plant nat-siRNAs reveals insights into their distribution, biogenesis and function.

    abstract:BACKGROUND:Many eukaryotic genomes encode cis-natural antisense transcripts (cis-NATs). Sense and antisense transcripts may form double-stranded RNAs that are processed by the RNA interference machinery into small interfering RNAs (siRNAs). A few so-called nat-siRNAs have been reported in plants, mammals, Drosophila, a...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2012-13-3-r20

    authors: Zhang X,Xia J,Lii YE,Barrera-Figueroa BE,Zhou X,Gao S,Lu L,Niu D,Chen Z,Leung C,Wong T,Zhang H,Guo J,Li Y,Liu R,Liang W,Zhu JK,Zhang W,Jin H

    更新日期:2012-01-01 00:00:00

  • Zinc finger nuclease-based double-strand breaks attenuate malaria parasites and reveal rare microhomology-mediated end joining.

    abstract:BACKGROUND:Genome editing of malaria parasites is key to the generation of live attenuated parasites used in experimental vaccination approaches. DNA repair in Plasmodium generally occurs only through homologous recombination. This has been used to generate transgenic parasites that lack one to three genes, leading to ...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-015-0811-1

    authors: Singer M,Marshall J,Heiss K,Mair GR,Grimm D,Mueller AK,Frischknecht F

    更新日期:2015-11-17 00:00:00

  • An evaluation of methods correcting for cell-type heterogeneity in DNA methylation studies.

    abstract:BACKGROUND:Many different methods exist to adjust for variability in cell-type mixture proportions when analyzing DNA methylation studies. Here we present the result of an extensive simulation study, built on cell-separated DNA methylation profiles from Illumina Infinium 450K methylation data, to compare the performanc...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-016-0935-y

    authors: McGregor K,Bernatsky S,Colmegna I,Hudson M,Pastinen T,Labbe A,Greenwood CM

    更新日期:2016-05-03 00:00:00

  • Inferring the functions of longevity genes with modular subnetwork biomarkers of Caenorhabditis elegans aging.

    abstract::A central goal of biogerontology is to identify robust gene-expression biomarkers of aging. Here we develop a method where the biomarkers are networks of genes selected based on age-dependent activity and a graph-theoretic property called modularity. Tested on Caenorhabditis elegans, our algorithm yields better biomar...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2010-11-2-r13

    authors: Fortney K,Kotlyar M,Jurisica I

    更新日期:2010-01-01 00:00:00

  • Transcriptional response to alcohol exposure in Drosophila melanogaster.

    abstract:BACKGROUND:Alcoholism presents widespread social and human health problems. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Genetic factors that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in hu...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/gb-2006-7-10-r95

    authors: Morozova TV,Anholt RR,Mackay TF

    更新日期:2006-01-01 00:00:00

  • Intraepithelial gamma delta T cells exposed by functional genomics.

    abstract::Epithelial tissues house gammadelta T cells, which are important for the mucosal immune system and may be involved in controlling malignancies, infections and inflammation. Whole-genome gene-expression analysis provides a new way to study the signals required for the activation of gammadelta T cells, their mode of act...

    journal_title:Genome biology

    pub_type: 杂志文章,评审

    doi:10.1186/gb-2001-2-11-reviews1031

    authors: Boismenu R,Havran WL

    更新日期:2001-01-01 00:00:00

  • The nuclear receptor ERβ engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading.

    abstract:BACKGROUND:The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNA-silencing pathways It exerts a pivotal role in microRNA maturation and activity and can modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. Estrogen receptor beta (ERβ) is endowed with oncosuppressive activities,...

    journal_title:Genome biology

    pub_type: 杂志文章

    doi:10.1186/s13059-017-1321-0

    authors: Tarallo R,Giurato G,Bruno G,Ravo M,Rizzo F,Salvati A,Ricciardi L,Marchese G,Cordella A,Rocco T,Gigantino V,Pierri B,Cimmino G,Milanesi L,Ambrosino C,Nyman TA,Nassa G,Weisz A

    更新日期:2017-10-06 00:00:00