Discovery of novel recurrent mutations and rearrangements in early T-cell precursor acute lymphoblastic leukemia by whole genome sequencing

·发布 2011年11月23日 ·更新 2012年6月26日

样本数

实验数

芯片平台

相关文献

实验描述

Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole genome sequencing of tumour and normal DNA from 12 children with ETP ALL and assessed the frequency of somatic alterations in 52 ETP and 42 non-ETP T-ALL samples by sequencing and DNA copy number analysis. ETP ALL was characterised by a high frequency of activating mutations in genes regulating cytokine receptor and Ras signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF); alterations disrupting haemopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1, EP300); and inactivating mutations in histone modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of mutation including DNM2, ECT2L and RELN. Ten of 12 ETP ALL cases harboured chromosomal rearrangements, several of which complex and resulted in the expression of novel chimeric in-frame fusion genes disrupting haemopoietic regulators. Thus, similar to myeloid malignancies, mutations that drive proliferation, impair differentiation and disrupt histone modification are hallmarks of ETP ALL. Moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haemopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL. Gene expression profiling was performed on 52 single diagnosis tumor samples. No control or reference samples were included.

参考文献

The BCL11B tumor suppressor is mutated across the major molecular subtypes of T-cell acute lymphoblastic leukemia.

Gutierrez A, Kentsis A, Sanda T, Holmfeldt L, Chen SC, Zhang J, Protopopov A, Chin L, Dahlberg SE, Neuberg DS, Silverman LB, Winter SS, Hunger SP, Sallan SE, Zha S, Alt FW, Downing JR, Mullighan CG, Look AT

PMID: 21878675

The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.

Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG

PMID: 22237106

芯片平台

A-GEOD-13158

[HT_HG-U133_Plus_PM] Affymetrix HT HG-U133+ PM Array Plate（52 例）

样本属性

cell type

tumor cells

Organism

Homo sapiens

实验信息

登记号

E-GEOD-28703

GEO 编号

GSE28703

实验类型

transcription profiling by array

物种

Homo sapiens

发布日期

2011年11月23日

更新日期

2012年6月26日

提交者

Jianming Wang、 James R Downing、 Daniel Alford、 Kimberly J Johnson、 William E Evans、 Stefan Roberts、 Dario Campana、 Richard K Wilson、 Meenakshi Devidas、 Kimberley P Dunsmore、 John E Dick、 Richard W Kriwacki、 Ching-Hon Pui、 John Easton、 Pankaj Gupta、 Stuart Winter、 Sergei Doulatov、 Xin Hong、 Debbie Payne-Turner、 Elaine Coustan-Smith、 Timothy J Ley、 Jared Becksfort、 Elisa Laurenti、 Giuseppe Basso、 Kathryn G Roberts、 Daniel J McGoldrick、 Jan Cools、 Charles G Mullighan、 Susan L Heatley、 Robert Huether、 Stanley B Pounds、 Michelle L Hermiston、 Jing Ma、 Kristin A Shimano、 Christopher C Harris、 Mignon L Loh、 Xiang Chen、 Faiyaz Notta、 Kerri Ochoa、 John C Obenauer、 Lucinda L Fulton、 Charles G Mullighan、 Maria Kleppe、 Michael Rusch、 Stephen Espy、 Elaine R Mardis、 Guangchun Song、 Deqing Pei、 Racquel Collins-Underwood、 Sheila A.Shurtleff、 Gang Wu、 Matthew Parker、 Brent Wood、 Robert S Fulton、 Susana C Raimondi、 Cheng Cheng、 Lei Wei、 Kolja Eppert、 David Zhao、 Shann-Ching Chen、 Stephen P Hunger、 Jinghui Zhang、 Kiran C Bobba、 Anatoly Ulyanov、 Li Ding、 Clayton W Naeve、 Michael I Barbato、 David J Dooling、 Charles Lu

外部链接

ArrayExpress 原始页 NCBI GEO：GSE28703

分析服务

Discovery of novel recurrent mutations and rearrangements in early T-cell precursor acute lymphoblastic leukemia by whole genome sequencing

联系地址

微信公众号