title: Molecular characterization of tumour heterogeneity and malignant mesothelioma cell differentiation by gene profiling.
abstract: Malignant mesothelioma is an aggressive tumour, characterized by a variable differentiation pattern and poor prognosis. At present, the clinical outcome in patients with malignant mesothelioma is mainly predicted by the morphological phenotype of the tumour. However, this conventional clinicopathological parameter is of limited value, partly because of the biological heterogeneity of this tumour and poor understanding of the regulatory mechanisms underlying the various patterns of growth. To elucidate the intrinsic molecular programmes that determine tumour differentiation, oligonucleotide arrays were used in an in vitro model of mesothelioma differentiation. The analysis of 2059 genes detected 102 genes that were significantly deregulated. Clustering of these genes into functional categories showed distinctive patterns for the two phenotypes, namely epithelioid and sarcomatoid. The molecular fingerprint of the sarcomatoid tumour component indicates overrepresentation of growth factor receptors and growth factor binding proteins, whereas epithelioid mesothelioma cells express other tumour-promoting factors involved in differentiation, metabolism, and regulation of apoptosis. These differences in the molecular phenotype may give a better basis for diagnosis and for designing novel therapies.
authors: Department of Laboratory Medicine, Division of Pathology, Huddinge University Hospital, F-46, Karolinska Institutet, S-141 86 Stockholm, Sweden.
authors: Xiaojuan
authors: X
authors: Sun
authors: Lei
authors: L
authors: Wei
authors: Johan
authors: J
authors: Lidén
authors: Gao
authors: G
authors: Hui
authors: Karin
authors: K
authors: Dahlman-Wright
authors: Anders
authors: A
authors: Hjerpe
authors: Katalin
authors: K
authors: Dobra
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation; D048429:Cell Size; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured