FPGS relapse-specific mutations in relapsed childhood acute lymphoblastic leukemia.

Scientific Reports
Sung-Liang YuYung-Li Yang

Abstract

Although the cure rate for childhood acute lymphoblastic leukemia (ALL) has exceeded 80% with contemporary therapy, relapsed ALL remains a leading cause of cancer-related death in children. Relapse-specific mutations can be identified by comprehensive genome sequencing and might have clinical significance. Applying whole-exome sequencing to eight triplicate samples, we identified in one patient relapse-specific mutations in the folylpolyglutamate synthetase (FPGS) gene, whose product catalyzes the addition of multiple glutamate residues (polyglutamation) to methotrexate upon their entry into the cells. To determine the prevalence of mutations of the FPGS mutations, and those of two important genes in the thiopurine pathway, NT5C2 and PRPS1, we studied 299 diagnostic and 73 relapsed samples in 372 patients. Three more FPGS mutants were identified in two patients, NT5C2 mutations in six patients, and PRPS1 mutants in two patients. One patient had both NT5C2 and PRPS1 mutants. None of these alterations were detected at diagnosis with a sequencing depth of 1000X, suggesting that treatment pressure led to increased prevalence of mutations during therapy. Functional characterization of the FPGS mutants showed that they directly resul...Continue Reading

References

Aug 11, 1981·Molecular and Cellular Biochemistry·J J McGuire, J R Bertino
Jan 13, 2006·The New England Journal of Medicine·Ching-Hon Pui, William E Evans
Feb 26, 2008·Leukemia & Lymphoma·Alan Kambiz Fotoohi, Freidoun Albertioni
Nov 29, 2008·Science·Charles G MullighanJames R Downing
Jun 26, 2009·The New England Journal of Medicine·Ching-Hon PuiMary V Relling
Jan 13, 2012·Nature·Jinghui ZhangCharles G Mullighan
May 23, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Allen Eng Juh YeohThuan Chong Quah
Aug 2, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Anthony V MoormanChristine J Harrison
Feb 5, 2013·Nature Genetics·Julia A MeyerWilliam L Carroll
May 30, 2015·Journal of Hematology & Oncology·Anna WojtuszkiewiczJacqueline Cloos
Aug 26, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ching-Hon PuiCharles G Mullighan
Oct 16, 2015·The New England Journal of Medicine·Stephen P Hunger, Charles G Mullighan
Sep 23, 2016·Proceedings of the National Academy of Sciences of the United States of America·Koichi OshimaAdolfo A Ferrando
Nov 23, 2016·Cancer Research·Ling-Wen DingH Phillip Koeffler

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Methods Mentioned

BETA
PCR
electrophoresis
Illumina sequencing
genotyping
flow cytometry
exome sequencing

Software Mentioned

Samtools
spec
GeneRead
CONSERTING
MEM
BWA
VarDict
QuantaSoft
Illumina Real Time Analysis ( RTA ) Pipeline
bcl2 fastq tool

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