Furthermore, the effects of miR-17-92 cluster on tumorigenicity of osteosarcoma cell lines were evaluated by in vitro assays. The relative expression of miR-17-92 cluster in osteosarcoma tissues was significantly higher than those in adjacent normal tissues (P=0.001). And there was a relationship between miR-17-92 cluster upregulation and advanced TNM stage of osteosarcoma patients (P=0.037). Moreover, higher miR-17-92 cluster expression dearly predicted poorer Recurrence-free survival (P smaller than 0.001) and Overall survival (P=0.002). In the multivariate analysis, high miR-17-92 BTSA1 cell line cluster expression was an independent prognostic factor for Recurrence-free survival (P smaller

than 0.001) and Overall survival (P=0.002). Furthermore, the cellular buy Navitoclax proliferation, invasion, and migration of osteosarcoma cell lines were significantly accelerated

by miR-17-92 cluster plasmid in vitro assays. Our findings showed that miR-17-92 cluster could serve as a promising marker for tumor recurrence and survival of osteosarcoma patients. Moreover, miR-17-92 cluster has been identified as a promoter for tumorigenicity of osteosarcoma cells, thus it might be a critical targeted therapy strategy for osteosarcoma.”
“Background Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder predisposing humans to cutaneous and uterine leiomyomas; in 20% of affected families, type 2 papillary renal cell cancers (PRCCII) also occur with aggressive course and poor prognosis. HLRCC results from heterozygous germline mutations in the tumour suppressor fumarate hydratase (FH) gene.\n\nMethods As part of the French National Cancer Institute (INCa) ‘Inherited predispositions to kidney cancer’ network, sequence analysis and a functional study of FH were preformed

in 56 families with clinically proven or suspected HLRCC and in 23 patients with isolated PRCCII (5 familial and 18 sporadic).\n\nResults The study identified 32 different germline FH mutations (15 missense, 6 frameshifts, 4 nonsense, 1 deletion/insertion, 5 splice site, and 1 complete deletion) in 40/56 (71.4%) families with proven or suspected HLRCC and in 4/23 (17.4%) selleck products probands with PRCCII alone, including 2 sporadic cases. 21 of these were novel and all were demonstrated as deleterious by significant reduction of FH enzymatic activity. In addition, 5 asymptomatic parents in 3 families were confirmed as carrying disease-causing mutations.\n\nConclusions This study identified and characterised 21 novel FH mutations and demonstrated that PRCCII can be the only one manifestation of HLRCC. Due to the incomplete penetrance of HLRCC, the authors propose to extend the FH mutation analysis to every patient with PRCCII occurring before 40 years of age or when renal tumour harbours characteristic histologic features, in order to discover previously ignored HLRCC affected families.