title: Clonal mutations in the cancer-associated fibroblasts: the case against genetic coevolution.
abstract: It is well established that carcinoma-associated fibroblasts (CAFs) differ phenotypically from fibroblasts associated with normal tissue, but the mechanisms underlying these differences remain controversial. Because CAFs can be propagated in vitro for extended periods and still maintain their cancer promoting phenotype, it has been proposed that they might have acquired somatic genetic alterations analogous to those observed in malignant epithelium. Whereas some investigators have reported frequent and profound genomic alterations in CAFs, other groups have found no such evidence. One striking common trait of those studies reporting frequent clonal somatic alterations in CAFs is the use of tissues and techniques which are well known to be highly prone to generating artefacts, such as limiting and poor quality DNA followed by highly multiplexed PCR-based analysis. We conclude that reported frequent clonal somatic mutations in CAFs are likely to be artefacts and are not the biological basis of the cancer promoting attributes of CAFs. [corrected]
authors.affiliation: VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. ian.campbell@petermac.org
authors.forename: Ian
authors.initials: I
authors.lastname: Campbell
authors.forename: Kornelia
authors.initials: K
authors.lastname: Polyak
authors.forename: Izhak
authors.initials: I
authors.lastname: Haviv
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D002450:Cell Communication; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor