A novel somatic mutation in ACD induces telomere lengthening and apoptosis resistance in leukemia cells

BMC Cancer
Jean-François SpinellaDaniel Sinnett

Abstract

The identification of oncogenic driver mutations has largely relied on the assumption that genes that exhibit more mutations than expected by chance are more likely to play an active role in tumorigenesis. Major cancer sequencing initiatives have therefore focused on recurrent mutations that are more likely to be drivers. However, in specific genetic contexts, low frequency mutations may also be capable of participating in oncogenic processes. Reliable strategies for identifying these rare or even patient-specific (private) mutations are needed in order to elucidate more personalized approaches to cancer diagnosis and treatment. Here we performed whole-exome sequencing on three cases of childhood pre-B acute lymphoblastic leukemia (cALL), representing three cytogenetically-defined subgroups (high hyperdiploid, t(12;21) translocation, and cytogenetically normal). We applied a data reduction strategy to identify both common and rare/private somatic events with high functional potential. Top-ranked candidate mutations were subsequently validated at high sequencing depth on an independent platform and in vitro expression assays were performed to evaluate the impact of identified mutations on cell growth and survival. We identified ...Continue Reading

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Citations

May 3, 2016·The Journal of Clinical Investigation·Morgan JonesIvan Maillard
Jan 7, 2020·Current Topics in Medicinal Chemistry·Xiaotian YuanDawei Xu
Sep 26, 2020·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·Karolina MalińskaTadeusz Dębniak
Feb 19, 2021·Cellular and Molecular Life Sciences : CMLS·Semih Can AkincilarVinay Tergaonkar

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Methods Mentioned

BETA
Exome Sequencing
PCR
flow cytometry
electrophoresis
X-ray
restriction fragment assay

Software Mentioned

Genome Analysis ToolKit ( GATK )
Ion Torrent
LifeScope Genomic Analysis
ANNOVAR
SAMtools
CONsensus
SNooPer

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