Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

Should pelvic exenteration for symptomatic relief in gynaecology malignancies be offered?

OBJECTIVE: To review the outcomes of pelvic exenterative surgery done with a palliative intent and evaluate its role in relapsed gynaecology malignancies.\n\nMETHOD: This is a retrospective cohort study between April 2009 and May 2012 in Oxford Gynaecological Cancer Centre. Patients were identified from the oncology surgical database.\n\nRESULTS: 18 patients were identified with a mean age 54 (26-79) years, who underwent surgery for symptomatic recurrent cancer. All except one patient had radiotherapy prior to surgery. 12 patients had cervical cancer, five had vulval cancer and one had endometrial cancer. About half of the patients had major surgical complications; however, majority was patients satisfied with the outcome.\n\nCONCLUSION: Pelvic exenteration in this context carries considerable morbidity and in this series achieved good symptom control with a mean overall survival of 11 months. Careful patient selection, adequate counselling and ongoing support are imperative of successful outcome