Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse
Virginia Perez-Andreu,Kathryn G. Roberts,Richard C. Harvey,Wenjian Yang,Cheng Cheng,Deqing Pei,Heng Xu,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Shuyu E,Joshua Yew Suang Lim,I. Ming Chen,Yiping Fan,Meenakshi Devidas,Michael J. Borowitz,Colton Smith,Geoffrey Neale,Esteban G. Burchard,Dara G. Torgerson,Federico Antillon Klussmann,Cesar Rolando Najera Villagran,Naomi J. Winick,Bruce M. Camitta,Elizabeth A. Raetz,Brent L. Wood,Feng Yue,William L. Carroll,Eric Larsen,W. Paul Bowman,Mignon L. Loh,Michael Dean,Deepa Bhojwani,Ching-Hon Pui,William E. Evans,Mary V. Relling,Stephen P. Hunger,Cheryl L. Willman,Charles G. Mullighan,Jun J. Yang +38 more
TLDR
In a genome-wide association study of 511 ALL cases and 6,661 non-ALL controls, a susceptibility locus for Ph-like ALL is identified and genotype at the GATA3 SNP was associated with early treatment response and risk of ALL relapse, providing insights into interactions between inherited and somatic variants and their role in ALL pathogenesis and prognosis.Abstract:
Recent genomic profiling of childhood acute lymphoblastic leukemia (ALL) identified a high-risk subtype with an expression signature resembling that of Philadelphia chromosome-positive ALL and poor prognosis (Ph-like ALL). However, the role of inherited genetic variation in Ph-like ALL pathogenesis remains unknown. In a genome-wide association study (GWAS) of 511 ALL cases and 6,661 non-ALL controls, we identified a susceptibility locus for Ph-like ALL (GATA3, rs3824662; P = 2.17 × 10(-14), odds ratio (OR) = 3.85 for Ph-like ALL versus non-ALL; P = 1.05 × 10(-8), OR = 3.25 for Ph-like ALL versus non-Ph-like ALL), with independent validation. The rs3824662 risk allele was associated with somatic lesions underlying Ph-like ALL (CRLF2 rearrangement, JAK gene mutation and IKZF1 deletion) and with variation in GATA3 expression. Finally, genotype at the GATA3 SNP was also associated with early treatment response and risk of ALL relapse. Our results provide insights into interactions between inherited and somatic variants and their role in ALL pathogenesis and prognosis.read more
Citations
More filters
Journal ArticleDOI
[Acute lymphoblastic leukemia: a genomic perspective].
TL;DR: An overview of the genomic perspective of ALL is provided, describing some strategies that contribute to the identification of biomarkers with potential clinical application.
Journal ArticleDOI
Therapy-related acute lymphoblastic leukemia: Where do we stand with regards to its definition and characterization?
TL;DR: All related to prior cytotoxic therapy (t-ALL) appears to be a distinct entity when compared to the de novo ALL, with characteristics including older age at the time of onset, female predominance and leukemia genetics enriched with KMT2A (MLL) gene rearrangement and chromosomes 5/7 abnormalities.
Journal ArticleDOI
Association of the independent polymorphisms in CDKN2A with susceptibility of acute lymphoblastic leukemia
TL;DR: It is indicated that two SNPs at CDKN2A locus are associated with ALL susceptibility independently mainly in Caucasians, and future large-scale studies are required to validate the associations in other ethnicities.
Journal ArticleDOI
Identification of a novel susceptibility locus at 16q23.1 associated with childhood acute lymphoblastic leukemia in Han Chinese
Yongyong Shi,Mulong Du,Yongjun Fang,Na Tong,Xiaowen Zhai,Xiaojing Sheng,Zhiqiang Li,Yao Xue,Jie Li,Haiyan Chu,Jianhua Chen,Zhijian Song,Jiawei Shen,Jue Ji,Xingwang Li,Zhibin Hu,Hongbing Shen,Jianfeng Xu,Meilin Wang,Zhengdong Zhang +19 more
TL;DR: It is suggested that WWOX plays an important role in the development of childhood All and new insights into the etiology of childhood ALL are provided.
References
More filters
Journal ArticleDOI
Inference of population structure using multilocus genotype data
TL;DR: Pritch et al. as discussed by the authors proposed a model-based clustering method for using multilocus genotype data to infer population structure and assign individuals to populations, which can be applied to most of the commonly used genetic markers, provided that they are not closely linked.
Journal ArticleDOI
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
Shaun Purcell,Shaun Purcell,Naomi R. Wray,Jennifer Stone,Jennifer Stone,Peter M. Visscher,Michael Conlon O'Donovan,Patrick F. Sullivan,Pamela Sklar,Pamela Sklar,Douglas M. Ruderfer,Andrew McQuillin,Derek W. Morris,Colm O'Dushlaine,Aiden Corvin,Peter Holmans,Stuart MacGregor,Hugh Gurling,Douglas Blackwood,Nicholas John Craddock,Michael Gill,Christina M. Hultman,Christina M. Hultman,George Kirov,Paul Lichtenstein,Walter J. Muir,Michael John Owen,Carlos N. Pato,Edward M. Scolnick,Edward M. Scolnick,David St Clair,Nigel Williams,Lyudmila Georgieva,Ivan Nikolov,Nadine Norton,Hywel Williams,Draga Toncheva,Vihra Milanova,Emma Flordal Thelander,Patrick Sullivan,Elaine Kenny,Emma M. Quinn,Khalid Choudhury,Susmita Datta,Jonathan Pimm,Srinivasa Thirumalai,Vinay Puri,Robert Krasucki,Jacob Lawrence,Digby Quested,Nicholas Bass,Caroline Crombie,Gillian Fraser,Soh Leh Kuan,Nicholas Walker,Kevin A. McGhee,Ben S. Pickard,P. Malloy,Alan W Maclean,Margaret Van Beck,Michele T. Pato,Helena Medeiros,Frank A. Middleton,Célia Barreto Carvalho,Christopher P. Morley,Ayman H. Fanous,David V. Conti,James A. Knowles,Carlos Ferreira,António Macedo,M. Helena Azevedo,Andrew Kirby,Andrew Kirby,Manuel A. R. Ferreira,Manuel A. R. Ferreira,Mark J. Daly,Mark J. Daly,Kimberly Chambert,Finny G Kuruvilla,Stacey Gabriel,Kristin G. Ardlie,Jennifer L. Moran +81 more
TL;DR: The extent to which common genetic variation underlies the risk of schizophrenia is shown, using two analytic approaches, and the major histocompatibility complex is implicate, which is shown to involve thousands of common alleles of very small effect.
Journal ArticleDOI
Diagnosis of multiple cancer types by shrunken centroids of gene expression
TL;DR: The method of “nearest shrunken centroids” identifies subsets of genes that best characterize each class, which was highly efficient in finding genes for classifying small round blue cell tumors and leukemias.
Journal ArticleDOI
Mapping and analysis of chromatin state dynamics in nine human cell types
Jason Ernst,Pouya Kheradpour,Pouya Kheradpour,Tarjei S. Mikkelsen,Noam Shoresh,Lucas D. Ward,Lucas D. Ward,Charles B. Epstein,Xiaolan Zhang,Li Wang,Robbyn Issner,Michael Coyne,Manching Ku,Manching Ku,Manching Ku,Timothy Durham,Manolis Kellis,Manolis Kellis,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein +20 more
TL;DR: This study presents a general framework for deciphering cis-regulatory connections and their roles in disease, and maps nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions.
Journal ArticleDOI
LocusZoom: regional visualization of genome-wide association scan results
Randall Pruim,Ryan P. Welch,Serena Sanna,Tanya M. Teslovich,Peter S. Chines,Terry P. Gliedt,Michael Boehnke,Gonçalo R. Abecasis,Cristen J. Willer +8 more
TL;DR: LocusZoom is a web-based plotting tool that provides fast visual display of GWAS results in a publication-ready format that visually displays regional information such as the strength and extent of the association signal relative to genomic position, local linkage disequilibrium (LD) and recombination patterns and the positions of genes in the region.
Related Papers (5)
Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia.
Charles G. Mullighan,Xiaoping Su,Jinghui Zhang,Ina Radtke,Letha A. Phillips,Christopher B. Miller,Jing Ma,Wei Liu,Cheng Cheng,Brenda A. Schulman,Brenda A. Schulman,Richard C. Harvey,Richard C. Harvey,I-Ming Chen,I-Ming Chen,Robert J. Clifford,William L. Carroll,Gregory H. Reaman,W. Paul Bowman,Meenakshi Devidas,Daniela S. Gerhard,Wenjian Yang,Mary V. Relling,Sheila A. Shurtleff,Dario Campana,Michael J. Borowitz,Ching-Hon Pui,Malcolm A. Smith,Stephen P. Hunger,Cheryl L. Willman,Cheryl L. Willman,James R. Downing +31 more
Targetable Kinase-Activating Lesions in Ph-like Acute Lymphoblastic Leukemia
Kathryn G. Roberts,Yongjin Li,Debbie Payne-Turner,Richard C. Harvey,Yung-Li Yang,Dehua Pei,Kelly McCastlain,Li Ding,Li Ding,Changxue Lu,Changxue Lu,Guangchun Song,Jing Ma,Jared Becksfort,Michael Rusch,S. C. Chen,John Easton,J. Cheng,Kristy Boggs,Natalia Santiago-Morales,Ilaria Iacobucci,Robert S. Fulton,Robert S. Fulton,Ji Wen,Marcus B. Valentine,Cheng Cheng,Steven W. Paugh,Meenakshi Devidas,Meenakshi Devidas,I-Ming Chen,S. Reshmi,S. Reshmi,Amy Smith,Erin Hedlund,Pankaj Gupta,Panduka Nagahawatte,Gang Wu,Xiang Chen,Donald Yergeau,Bhavin Vadodaria,Heather L. Mulder,Naomi J. Winick,Eric Larsen,William L. Carroll,William L. Carroll,Nyla A. Heerema,Andrew J. Carroll,G. Grayson,Sarah K. Tasian,Andrew S. Moore,F. Keller,Melissa Frei-Jones,J. A. Whitlock,Elizabeth A. Raetz,Deborah L. White,Timothy P. Hughes,J. M. Guidry Auvil,Malcolm A. Smith,Malcolm A. Smith,Guido Marcucci,Clara D. Bloomfield,Krzysztof Mrózek,Jessica Kohlschmidt,Jessica Kohlschmidt,Wendy Stock,Steven M. Kornblau,Marina Konopleva,Elisabeth Paietta,Ching-Hon Pui,Sima Jeha,Mary V. Relling,William E. Evans,Daniela S. Gerhard,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Elaine R. Mardis,Richard K. Wilson,Mignon L. Loh,Mignon L. Loh,James R. Downing,James R. Downing,Stephen P. Hunger,Stephen P. Hunger,Cheryl L. Willman,Cheryl L. Willman,Jinghui Zhang,Charles G. Mullighan,Charles G. Mullighan +87 more
A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study
Monique L. den Boer,Marjon van Slegtenhorst,Renee X. de Menezes,Renee X. de Menezes,Meyling Cheok,Jessica Buijs-Gladdines,Susan T C J M Peters,Laura J. C. M. van Zutven,H. Berna Beverloo,Peter J. van der Spek,Gaby Escherich,Martin A. Horstmann,Gritta Janka-Schaub,Willem A. Kamps,William E. Evans,Rob Pieters +15 more
Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia
Richard C. Harvey,Richard C. Harvey,Charles G. Mullighan,I-Ming Chen,I-Ming Chen,Walker Wharton,Fady M. Mikhail,Andrew J. Carroll,Andrew J. Carroll,Huining Kang,Wei Liu,Kevin K. Dobbin,Malcolm A. Smith,William L. Carroll,William L. Carroll,Meenakshi Devidas,Meenakshi Devidas,W. Paul Bowman,Bruce M. Camitta,Bruce M. Camitta,Gregory H. Reaman,Gregory H. Reaman,Stephen P. Hunger,Stephen P. Hunger,James R. Downing,Cheryl L. Willman,Cheryl L. Willman +26 more
The genomic landscape of hypodiploid acute lymphoblastic leukemia
Linda Holmfeldt,Lei Wei,Ernesto Diaz-Flores,Michael Walsh,Jinghui Zhang,Li Ding,Debbie Payne-Turner,Michelle L. Churchman,Anna Andersson,Shann Ching Chen,Kelly McCastlain,Jared Becksfort,Jing Ma,Gang Wu,Samir Patel,Susan L. Heatley,Letha A. Phillips,Guangchun Song,John Easton,Matthew Parker,Xiang Chen,Michael Rusch,Kristy Boggs,Bhavin Vadodaria,Erin Hedlund,Christina D. Drenberg,Sharyn D. Baker,Deqing Pei,Cheng Cheng,Robert Huether,Charles Lu,Robert S. Fulton,Lucinda Fulton,Yashodhan Tabib,David J. Dooling,Kerri Ochoa,Mark D. Minden,Ian D. Lewis,L. Bik To,Paula Marlton,Andrew W. Roberts,Gordana Raca,Wendy Stock,Geoffrey Neale,Hans G. Drexler,Ross A. Dickins,David W. Ellison,Sheila A. Shurtleff,Ching-Hon Pui,Raul C. Ribeiro,Meenakshi Devidas,Andrew J. Carroll,Nyla A. Heerema,Brent L. Wood,Michael J. Borowitz,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Susana C. Raimondi,Elaine R. Mardis,Richard K. Wilson,James R. Downing,Stephen P. Hunger,Mignon L. Loh,Charles G. Mullighan +63 more