In Modern Pathology this week, researchers from the Seoul National University in South Korea report on the association between the patterns of promoter CpG island methylation of breast cancer subtypes and cancer stem cell phenotypes. The team analyzed methylation status of 15 promoter CpG island loci involved in breast cancer progression, and determined their cancer stem cell phenotypes. They found that "the number of CpG island loci methylated differed significantly between subtypes, and was highest in the luminal-HER2 subtype and lowest in the basal-like subtype. Methylation frequencies and levels in 12 of the 15 genes differed significantly between subtypes, and the basal-like subtype had significantly lower methylation frequencies and levels in nine of the genes than the other subtypes." These findings suggest that breast cancer subtypes have distinct methylation patterns and that these patterns are associated with different stem cell phenotypes, the authors add.
Also in Modern Pathology, a team of French researchers elucidates the role of the mTOR pathway in leiomyosarcomas and pleomorphic sarcomas. The team assessed PTEN level and protein expression as well as the activation of downstream pathways, in a large series of sarcomas. They observed PTEN partial genomic loss in 46 percent of the tumors and a loss of protein expression in up to 68 percent of the tumors. "PTEN mutations were rare, with only 4 point mutations in the 65 samples studied," the authors write. "Subsequent activation of AKT and mTOR pathways was only observed in 2 out of 3 of PTEN-deleted tumors. On the other hand, RICTOR, a major component of the mTOR complex 2, was significantly overexpressed in well-differentiated leiomyosarcomas." The results suggest a link between RICTOR over-expression and leiomyosarcomas oncogenesis, the researchers add.
Finally in Modern Pathology this week, Macher-Goeppinger et al. report on the molecular heterogeneity of TFE3 activation in renal cell carcinomas. The team examined TFE3 expression and underlying genetic alterations in a series of renal cell carcinomas with long-term follow-up information. They found that five out of a total 876 tumors had TFE3 translocations, but that 9 percent of all renal cell carcinoma samples showed some degree of TFE3 reactivity. "Interestingly, these cases were associated with high nuclear grade, greater tumor extent and metastatic disease as well as an unfavorable patient outcome on uni- and multivariate analysis," the authors write. "Fluorescence in situ hybridisation revealed TFE3 amplifications as an additional, novel mechanism leading to increased TFE3 expression levels."
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