UNASSIGNED: Epigenetic changes through altered DNA methylation have been implicated in critical aspects of @entity5 progression, and have been extensively studied in a variety of @entity5 types. In contrast, our current knowledge of the aberrant genomic DNA methylation in @entity5 -associated fibroblasts (TAFs) or other stromal cells that act as critical coconspirators of @entity5 progression is very scarce. To address this gap of knowledge, we conducted genome-wide DNA methylation profiling on lung TAFs and paired control fibroblasts (CFs) from @entity1149 @entity1 using the HumanMethylation450 microarray. We found widespread DNA hypomethylation concomitant with focal gain of DNA methylation in TAFs compared to CFs. The aberrant DNA methylation landscape of TAFs had a global impact on gene expression and a selective impact on the @entity2533 pathway. The latter included promoter hypermethylation-associated @entity7379 silencing, which was associated with hyperresponsiveness to exogenous @entity2533 in terms of contractility and extracellular matrix deposition. In turn, activation of CFs with exogenous @entity2533 partially mimicked the epigenetic alterations observed in TAFs, suggesting that @entity2533 may be necessary but not sufficient to elicit such alterations. Moreover, integrated pathway-enrichment analyses of the DNA methylation alterations revealed that a fraction of TAFs may be bone marrow-derived fibrocytes. Finally, survival analyses using DNA methylation and gene expression datasets identified aberrant DNA methylation on the @entity58643 promoter sequence as a prognostic factor in @entity1149 @entity1 . Our findings shed light on the unique origin and molecular alterations underlying the aberrant phenotype of lung TAFs, and identify a stromal biomarker with potential clinical relevance.

Aberrant DNA methylation in XXXX -associated fibroblasts.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity7379 :: ('4088', 'Gene') :: ['SMAD3'] @entity58643 :: ('128178', 'Gene') :: ['EDARADD'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity1149 :: ('MESH:D002289', 'Disease') :: ['non-small cell lung cancer'] @entity2533 :: ('7040', 'Gene') :: ['TGF-b', 'TGF-b1']
@entity1149 :: (MESH:D002289,Disease) :: ['non-small cell lung cancer']
