A high-throughput distributed DNA sequence analysis and database system

2001 ◽  
Vol 40 (2) ◽  
pp. 464-486 ◽  
Author(s):  
J. T. Inman ◽  
H. R. Flores ◽  
G. D. May ◽  
J. W. Weller ◽  
C. J. Bell
Keyword(s):  
Sequence Analysis ◽  
Dna Sequence ◽  
High Throughput ◽  
Database System ◽  
Dna Sequence Analysis

scholarly journals Identification of Driver and Passenger Mutations of FLT3 by High-Throughput DNA Sequence Analysis and Functional Assessment of Candidate Alleles

Cancer Cell ◽  
2007 ◽  
Vol 12 (6) ◽  
pp. 501-513 ◽  
Author(s):  
Stefan Fröhling ◽  
Claudia Scholl ◽  
Ross L. Levine ◽  
Marc Loriaux ◽  
Titus J. Boggon ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Dna Sequence ◽  
High Throughput ◽  
Functional Assessment ◽  
Dna Sequence Analysis ◽  
Passenger Mutations

scholarly journals High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria

Gut Microbes ◽  
2013 ◽  
Vol 4 (2) ◽  
pp. 125-135 ◽  
Author(s):  
Matthew J. Hamilton ◽  
Alexa R. Weingarden ◽  
Tatsuya Unno ◽  
Alexander Khoruts ◽  
Michael J. Sadowsky
Keyword(s):  
Sequence Analysis ◽  
Gut Microbiota ◽  
Dna Sequence ◽  
High Throughput ◽  
Dna Sequence Analysis ◽  
Fecal Bacteria

Identification of Driver and Passenger Mutations of FLT3 by High-Throughput DNA Sequence Analysis and Functional Assessment of Candidate Alleles.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 206-206
Author(s):  
Stefan Frohling ◽  
Claudia Scholl ◽  
Ross L. Levine ◽  
Marc Loriaux ◽  
Titus J. Boggon ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Dna Sequence ◽  
High Throughput ◽  
Functional Assessment ◽  
Kinase Activity ◽  
Dna Sequence Analysis ◽  
Activation Loop ◽  
Juxtamembrane Domain ◽  
Genomic Alterations ◽  
Activating Mutations

Abstract Activating mutations in the juxtamembrane domain or the activation loop of the receptor tyrosine kinase FLT3 occur in many cases of acute myeloid leukemia (AML), but it is not known whether genomic alterations outside these regions contribute to leukemogenesis. High-throughput DNA sequence analysis has provided insights into the mutational profiles of various cancers and represents a promising strategy for the identification of novel therapeutic targets. However, recognizing the subset of genomic alterations that are functionally relevant has proven difficult. We used a high-throughput platform to interrogate the entire FLT3 coding sequence in a cohort of 222 adult AML patients without known FLT3 mutations and experimentally tested the functional consequences of each candidate leukemogenic allele by exogenous expression in BaF3 cells. DNA sequencing detected nine non-synonymous sequence variants in six exons that were not known single-nucleotide polymorphisms. Functional assessment of these alleles identified four novel activating mutations in the extracellular domain, the juxtamembrane domain, and the activation loop that induced constitutive kinase activity, differentially activated downstream signaling pathways, and conferred varying sensitivity to pharmacologic FLT3 inhibition. In contrast, the remaining five alleles, including mutations in highly conserved, key functional domains of FLT3, were not associated with increased kinase activity and aberrant signal transduction. These findings support the concept that acquired mutations in cancer may not contribute to malignant transformation, and underscore the importance of functional validation of candidate alleles discovered using high-throughput genomic screens, to distinguish between ‘driver’ mutations underlying cancer development, and biologically neutral ‘passenger’ alterations.

Sign in / Sign up

Export Citation Format

Share Document