Specific oncogene activation of the cell of origin in mucosal melanoma.

Mucosal melanoma (MM) is a deadly cancer derived from mucosal melanocytes. To test the consequences of MM genetics, we develop a zebrafish model in which all melanocytes experience CCND1 expression and loss of PTEN and TP53. Surprisingly, melanoma only develops from melanocytes lining internal organs, analogous to the location of patient MM.

Recurrent oncogenic ZC3H18 mutations stabilize endogenous retroviral RNA.

Endogenous retroviral (ERV) RNA is highly expressed in cancer, although the molecular causes and consequences remain unknown. We found that ZC3H18 (Z18), a component of multiple nuclear RNA surveillance complexes, has recurrent truncating mutations in cancer. We show that Z18 mutations are oncogenic and that Z18 plays an evolutionarily conserved role in nuclear RNA surveillance of ERV RNA.

Oncogenic mutations impede nuclear RNA surveillance.

RNA surveillance pathways detect and degrade defective transcripts to ensure RNA fidelity. We found that disrupted nuclear RNA surveillance is oncogenic. Cyclin-dependent kinase 13 () is mutated in melanoma, and patient-mutated accelerates zebrafish melanoma.

Socioeconomic status and stroke.

This paper reviews the current evidence for the association between socioeconomic status and stroke incidence, survival, mortality, and other outcomes. The evidence is strongest for mortality and incidence of stroke, with high rates of stroke in low socioeconomic groups being a consistent finding. Low socioeconomic groups also have lower survival and greater stroke severity than high socioeconomic groups, although there is less evidence for this association.