In Clinical Cancer Research this week, researchers in Scandinavia and the US report that their molecular profiling of primary melanoma revealed low-grade and high-grade forms of the disease. The team analyzed RNA expression, oncogenic mutations, histomorphometry, and survival data from 223 archival primary melanomas, and found that the previously established four-class structure of primary melanoma converged into two larger prognostic and phenotypic groups. "We used the metastatic lesions to develop a binary subtype-based signature capable of distinguishing between 'high' and 'low' grade forms of the disease," the team says. "Compared with low-grade tumors, high-grade primary melanomas were significantly associated with increased tumor thickness, mitotic rate, ulceration, and poorer relapse-free, and overall survival. High-grade melanomas exhibited elevated levels of proliferation and BRCA1/DNA damage signaling genes, whereas low-grade lesions harbored higher expression of immune genes."
Also in Clinical Cancer Research this week, an international team of researchers says that the RAS-GTPase-activating protein DAB2IP is a medulloblastoma tumor suppressor and can be used a positive prognostic marker. The team conducted a meta-analysis of mouse and human medulloblastoma gene expression datasets and found that DAB2IP expression is repressed in these tumors by EZH2-induced trimethylation. "We observed that reduced DAB2IP expression correlates significantly with a poor overall survival of patients with medulloblastoma, independent of metastatic stage," the authors write. "We showed that ectopic DAB2IP expression enhances stress-induced apoptosis in medulloblastoma cells and that reduced expression of DAB2IP in medulloblastoma cells conveys resistance to irradiation-induced cell death."
Finally in Clinical Cancer Research this week, researchers in Singapore report that patients with oligodendroglial tumors have better survival because those tumors have progenitor-like traits. The team studied expression data from patient-derived glioma-propagating cells, or GPCs, and developed a gene signature to distinguish oligodendroglial GPCs from glioblastoma multiforme GPCs. "By adapting a method in glioma biology, the Connectivity Map, we interrogated its strength of association in public clinical databases," the authors write. "We validated the top-ranking signaling pathways Wnt, Notch, and TGFβ, in GPCs and primary tumor specimens." They observed that oligodendroglial GPC features and lower tumor grade correlated with better prognosis for patients, and patients with better prognosis had proneural tumors whil patients with poor survival had mesenchymal tumors. "GPCs are clinically relevant," the team adds. "The more favorable prognosis of oligodendroglial tumors over GBM could be recapitulated transcriptomically at the GPC level, underscoring the relevance of this cellular model."