Genomic and transcriptomic analyses identify a prognostic gene signature and predict response to therapy in pleural and peritoneal mesothelioma.

Malignant mesothelioma is an aggressive cancer with limited treatment options and poor prognosis. A better understanding of mesothelioma genomics and transcriptomics could advance therapies. Here, we present a mesothelioma cohort of 122 patients along with their germline and tumor whole-exome and tumor RNA sequencing data as well as phenotypic and drug response information. We identify a 48-gene prognostic signature that is highly predictive of mesothelioma patient survival, including CCNB1, the expression of which is highly predictive of patient survival on its own. In addition, we analyze the transcriptomics data to study the tumor immune microenvironment and identify synthetic-lethality-based signatures predictive of response to therapy. This germline and somatic whole-exome sequencing as well as transcriptomics data from the same patient are a valuable resource to address important biological questions, including prognostic biomarkers and determinants of treatment response in mesothelioma.

Reduced expression of CAMTA1 correlates with adverse outcome in neuroblastoma patients.

PURPOSE: A distal portion of 1p is frequently deleted in human neuroblastomas, and it is generally assumed that this region harbors at least one gene relevant for neuroblastoma development. A 1p36.3 commonly deleted region, bordered by D1S2731 and D1S214 has been defined. The present study surveys whether expression of genes mapping to this region is associated with tumor behavior. EXPERIMENTAL DESIGN: Candidate genes localized within the deleted region were identified by sequence data analysis. Their expression was assessed in a cohort of 49 primary neuroblastomas using cDNA microarray analysis. Gene expression patterns associated with known prognostic markers and patient outcome were further evaluated by quantitative real-time reverse transcription-PCR in a cohort of 102 neuroblastomas. RESULTS: The commonly deleted region spans 261 kb and encompasses two genes, FLJ10737 and CAMTA1. We found no evidence for an association of FLJ10737 expression with established prognostic variables or outcome. In contrast, low CAMTA1 expression characterized tumors with 1p deletion, MYCN amplification, and advanced tumor stages 3 and 4. Moreover, low CAMTA1 expression was significantly associated with poor outcome (P < 0.001). In multivariate analysis of event-free survival, the prognostic information of low CAMTA1 expression was independent of 1p status, MYCN status, tumor stage, and age of the patient at diagnosis (hazard ratio, 3.52; 95% confidence interval, 1.21-10.28; P = 0.02). CONCLUSIONS: Our data suggest that assessment of CAMTA1 expression may improve the prognostic models for neuroblastoma and that it will be important to define the biological function of CAMTA1 in this disease.