title: Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers.
abstract: Tyrosine kinases are major regulators of signal transduction cascades involved in cellular proliferation and have important roles in tumorigenesis. We have recently analyzed the tyrosine kinase gene family for alterations in human colorectal cancers and identified somatic mutations in seven members of this gene family. In this study we have used high-throughput sequencing approaches to further evaluate this subset of genes for genetic alterations in other human tumors. We identified somatic mutations in GUCY2F, EPHA3, and NTRK3 in breast, lung, and pancreatic cancers. Our results implicate these tyrosine kinase genes in the pathogenesis of other tumor types and suggest that they may be useful targets for diagnostic and therapeutic intervention in selected patients.
authors.affiliation: The Ludwig Center for Cancer Genetics and Therapeutics, The Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland 21231, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Wood
authors.forename: Eric S
authors.initials: ES
authors.lastname: Calhoun
authors.forename: Natalie
authors.initials: N
authors.lastname: Silliman
authors.forename: Janine
authors.initials: J
authors.lastname: Ptak
authors.forename: Steve
authors.initials: S
authors.lastname: Szabo
authors.forename: Steve M
authors.initials: SM
authors.lastname: Powell
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
authors.forename: Tian-Li
authors.initials: TL
authors.lastname: Wang
authors.forename: Hai
authors.initials: H
authors.lastname: Yan
authors.forename: Adi
authors.initials: A
authors.lastname: Gazdar
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kern
authors.forename: Len
authors.initials: L
authors.lastname: Pennacchio
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.forename: Victor E
authors.initials: VE
authors.lastname: Velculescu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D036121:Receptor, EphA3; D020812:Receptor, trkC / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D011956:Receptors, Cell Surface; C491718:EPHA3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D036121:Receptor, EphA3; D020812:Receptor, trkC; C484784:GUCY2F protein, human; D006162:Guanylate Cyclase