Publikation

Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate alleles

Wissenschaftlicher Artikel/Review - 01.12.2007

Bereiche
PubMed
DOI

Zitation
Fröhling S, Jiang J, Schittenhelm M, Lee B, Griffin J, Stone R, Heinrich M, Deininger M, Druker B, Golub T, Teckie S, Ebert B, Scholl C, Levine R, Loriaux M, Boggon T, Bernard O, Berger R, Döhner H, Döhner K, Gilliland D. Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate alleles. Cancer Cell 2007; 12:501-13.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Cancer Cell 2007; 12
Veröffentlichungsdatum
01.12.2007
ISSN (Druck)
1535-6108
Seiten
501-13
Kurzbeschreibung/Zielsetzung

Mutations in the juxtamembrane and kinase domains of FLT3 are common in AML, but it is not known whether alterations outside these regions contribute to leukemogenesis. We used a high-throughput platform to interrogate the entire FLT3 coding sequence in AML patients without known FLT3 mutations and experimentally tested the consequences of each candidate leukemogenic allele. This approach identified gain-of-function mutations that activated downstream signaling and conferred sensitivity to FLT3 inhibition and alleles that were not associated with kinase activation, including mutations in the catalytic domain. These findings support the concept that acquired mutations in cancer may not contribute to malignant transformation and underscore the importance of functional studies to distinguish "driver" mutations underlying tumorigenesis from biologically neutral "passenger" alterations.