Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia

·发布 2016年2月17日 ·更新 2016年3月17日

样本数

实验数

实验描述

Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17) leading to formation of PML-RARA fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, while mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large scale activation of gene expression and reduced in vitro differentiation potential. Studying the effects of silensing ARID1B gene in NB4 cell lines

样本属性

cell-line

NB4

organism

Homo sapiens

shRNA

control/non-target shRNA, shRNA targeting human ARID1B gene

实验信息

登记号

E-GEOD-77946

GEO 编号

GSE77946, SRP070153

实验类型

RNA-seq of coding RNA

物种

Homo sapiens

发布日期

2016年2月17日

更新日期

2016年3月17日

提交者

Michael Lübbert、 Yasunobu Nagata、 Tobias Ma、 Kenichi Yoshida、 Noreen Fulton、 Masashi Sanada、 Jairo Matthews、 Hwei-Fang Tien、 Norimichi Hattori、 Yuichi Shiraishi、 Janani Sundaresan、 Richard A Larson、 Michael Lill、 Li-Zhen Liu、 Kar-Tong Tan、 Wolf-Karsten Hoffmann、 Henry Yang、 Saravanan Ganesan、 H P Koeffler、 Manoj Garg、 Shahrbano Rostami、 Steven M Kornblau、 Seishi Ogawa、 Lee-Yung Shih、 Anand Mayakonda、 Kamran Alimoghaddam、 Ezhilarasi Chendamarai、 Deepika Kanojia、 Satoru Miyano、 Michel Heuser、 Bayard L Powell、 Ardeshir Ghavamzadeh、 Ling-Wen Ding、 Ming-Chung Kuo、 Gregory Malnassy、 Vikram Mathews、 Wenwen Chien、 Phillip H Koeffler、 Daniel Nowak、 Torsten Haferlach、 Wee J Chng、 Pavithra Shyamsunder、 Takayuki Ikezoe、 Vikas Madan、 Andrea Biondi、 Tamara Aplermann、 Arnold Ganser、 Wendy Stock、 Lin Han、 Hagop M Kantarjian、 Qiao-Yang Sun、 Hsin-An Hou、 Maya Koren-Michowitz

外部链接

ArrayExpress 原始页 NCBI GEO：GSE77946, SRP070153

分析服务

Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia

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