Current paradigms hold that @entity2 arise from pleuripotent stem cells capable of differentiation into one or several histological types. These paradigms suggest @entity2 cell ontogeny is determined by consequences of gene expression that recapitulate events important in embryonic lung development. Using oligonucleotide microarrays, we acquired gene profiles from 32 microdissected @entity1149 . We determined the 100 top-ranked marker genes for @entity420 , squamous cell, large cell, and @entity4303 using nearest neighbor analysis. Results were validated by immunostaining for 11 selected proteins using a tissue microarray representing 80 @entity5 . Gene expression data of lung development were accessed from a publicly available dataset generated with the @entity19 Mu11k genome microarray. Self-organized mapping identified two temporally distinct clusters of @entity19 orthologues. Supervised clustering of lung development data showed large-cell @entity189 gene orthologues were in a cluster expressed in pseudoglandular and canalicular stages whereas @entity420 homologues were predominantly in a cluster expressed later in the terminal sac and alveolar stages of @entity19 lung development. Representative large-cell genes ( @entity41716 , @entity53645 , @entity30653 , @entity11953 , @entity4698 ) are expressed in the nucleus and are associated with cell cycle and proliferation. In contrast, @entity420 genes are associated with lung-specific transcription pathways ( @entity44472 , @entity12625 ), cell adhesion, and signal transduction. In sum, @entity1149 histology gene profiles suggest mechanisms relevant to ontogeny and clinical course. @entity420 genes are associated with differentiation and glandular formation whereas large-cell genes are associated with proliferation and differentiation arrest. The identification of developmentally regulated pathways active in tumorigenesis provides insights into lung carcinogenesis and suggests early steps may differ according to the eventual @entity5 morphology.

XXXX molecular signatures recapitulate lung developmental pathways.

@entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity53645 :: ('17865(Tax:10090)', 'Gene') :: ['MYBL2'] @entity1149 :: ('MESH:D002289', 'Disease') :: ['non-small-cell lung tumors'] @entity2 :: ('MESH:D008175', 'Disease') :: ['lung carcinomas', 'lung tumor'] @entity189 :: ('MESH:D002277', 'Disease') :: ['carcinoma'] @entity44472 :: ('20388(Tax:10090)', 'Gene') :: ['SFTPB'] @entity4698 :: ('18538(Tax:10090)', 'Gene') :: ['PCNA'] @entity12625 :: ('22130(Tax:10090)', 'Gene') :: ['TTF-1'] @entity11953 :: ('12567(Tax:10090)', 'Gene') :: ['CDK4'] @entity4303 :: ('MESH:D002276', 'Disease') :: ['carcinoid'] @entity41716 :: ('13557(Tax:10090)', 'Gene') :: ['E2F3'] @entity30653 :: ('15182(Tax:10090)', 'Gene') :: ['HDAC2'] @entity420 :: ('MESH:D000230', 'Disease') :: ['Adenocarcinoma', 'adenocarcinoma']
@entity1149 :: (MESH:D002289,Disease) :: ['Non-small-cell lung cancer']
