title: Intratumor versus intertumor heterogeneity in gene expression profiles of soft-tissue sarcomas.
abstract: Soft-tissue sarcomas (STSs) constitute more than 30 histologic entities. In addition, within each entity, tumors are often heterogeneous in macroscopic features, genetic alterations, microscopic appearance, and clinical course. Therefore, there has been concern about whether a single tumor sample can provide a gene expression profile representative of the entire tumor. We used 27-k cDNA microarray slides to assess the importance of intratumor versus intertumor heterogeneity of the gene expression profiles of 2 morphologically heterogeneous STSs. Multiple pieces of tumor (8 and 10 pieces) were obtained from a myxoid variant of malignant fibrous histiocytoma (MFH) and a leiomyosarcoma (LMS), respectively, and the expression patterns were compared with single tumor samples from 20 MFHs and 16 LMSs. Hierarchical clustering analysis of the expression profiles showed that samples from the same tumor clustered together. The average intratumor distance was considerably shorter than the average intertumor distance in both LMS and MFH. In addition, tumor subclusters that distinguished different macroscopic parts of the tumor could be discerned. We concluded that intratumor variability exists but that accurate gene expression profiling also could be obtained using single samples from a large STS.
authors.affiliation: Department of Oncology, Lund University, Lund, Sweden. Princy.Francis@onk.lu.se)
authors.forename: Princy
authors.initials: P
authors.lastname: Francis
authors.forename: Josefin
authors.initials: J
authors.lastname: Fernebro
authors.forename: Patrik
authors.initials: P
authors.lastname: Edén
authors.forename: Anna
authors.initials: A
authors.lastname: Laurell
authors.forename: Anders
authors.initials: A
authors.lastname: Rydholm
authors.forename: Henryk A
authors.initials: HA
authors.lastname: Domanski
authors.forename: Thomas
authors.initials: T
authors.lastname: Breslin
authors.forename: Cecilia
authors.initials: C
authors.lastname: Hegardt
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: Mef
authors.initials: M
authors.lastname: Nilbert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D012509:Sarcoma / Q000098:blood supply / Q000145:classification / Q000235:genetics* / Q000473:pathology