title: Three-dimensional mRNA measurements reveal minimal regional heterogeneity in esophageal squamous cell carcinoma.
abstract: The classic tumor clonal evolution theory postulates that cancers change over time to produce unique molecular subclones within a parent neoplasm, presumably including regional differences in gene expression. More recently, however, this notion has been challenged by studies showing that tumors maintain a relatively stable transcript profile. To examine these competing hypotheses, we microdissected discrete subregions containing approximately 3000 to 8000 cells (500 to 1500 μm in diameter) from ex vivo esophageal squamous cell carcinoma (ESCC) specimens and analyzed transcriptomes throughout three-dimensional tumor space. Overall mRNA profiles were highly similar in all 59 intratumor comparisons, in distinct contrast to the markedly different global expression patterns observed in other dissected cell populations. For example, normal esophageal basal cells contained 1918 and 624 differentially expressed genes at a greater than twofold level (95% confidence level of <5% false positives), compared with normal differentiated esophageal cells and ESCC, respectively. In contrast, intratumor regions had only zero to four gene changes at a greater than twofold level, with most tumor comparisons showing none. The present data indicate that, when analyzed using a standard array-based method at this level of histological resolution, ESCC contains little regional mRNA heterogeneity.
authors.affiliation: Pathogenetics Unit, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Wusheng
authors.initials: W
authors.lastname: Yan
authors.forename: Joanna
authors.initials: J
authors.lastname: Shih
authors.forename: Jaime
authors.initials: J
authors.lastname: Rodriguez-Canales
authors.forename: Michael A
authors.initials: MA
authors.lastname: Tangrea
authors.forename: Audrey
authors.initials: A
authors.lastname: Player
authors.forename: Lixia
authors.initials: L
authors.lastname: Diao
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Michael R
authors.initials: MR
authors.lastname: Emmert-Buck
authors.forename: Heidi S
authors.initials: HS
authors.lastname: Erickson
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D018740:Genetic Heterogeneity; D006801:Humans; D042282:Microdissection; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D012333:RNA, Messenger