Genetic changes in tumour microenvironments

摘要: Numerous in vitro and vivo studies have established that carcinoma-associated fibroblasts differ phenotypically from associated with normal tissue but the mechanisms underlying these differences are unclear. Since can be propagated for extended periods still maintain their cancer-promoting phenotype, some investigators proposed they might acquired somatic genetic alterations analogous to those observed malignant epithelium. Early molecular appeared validate this hypothesis by demonstrating remarkably high frequencies of clonal fibroblasts, including loss heterozygosity, gene amplification, point mutations tumour suppressor genes such as TP53 PTEN. The initial excitement paradigm-changing overshadowed concerns there may been a more mundane explanation observations. In addition fact data would necessarily invoke an unlikely scenario simultaneous generation two symbiotic malignancies, subsequent found no evidence frequent genomic aberrations. One striking common trait reporting is use tissues techniques which well known highly prone generating artefacts limiting poor quality DNA followed multiplexed PCR-based analyses. It now clear not biological basis attributes fibroblasts.