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PurposeTo identify molecular subclasses of clear cell ovarian carcinoma (CCOC) and assess their impact on clinical presentation and outcomes.Experimental designWe profiled 421 primary CCOCs that passed quality control using a targeted deep sequencing panel of 163 putative CCOC driver genes and whole transcriptome sequencing of 211 of these tumors. Molecularly defined subgroups were identified and tested for association with clinical characteristics and overall survival.ResultsWe detected a putative somatic driver mutation in at least one candidate gene in 95% (401/421) of CCOC tumors including ARID1A (in 49% of tumors), PIK3CA (49%), TERT (20%), and TP53 (16%). Clustering of cancer driver mutations and RNA expression converged upon two distinct subclasses of CCOC. The first was dominated by ARID1A-mutated tumors with enriched expression of canonical CCOC genes and markers of platinum resistance; the second was largely comprised of tumors with TP53 mutations and enriched for the expression of genes involved in extracellular matrix organization and mesenchymal differentiation. Compared with the ARID1A-mutated group, women with TP53-mutated tumors were more likely to have advanced-stage disease, no antecedent history of endometriosis, and poorer survival, driven by their advanced stage at presentation. In women with ARID1A-mutated tumors, there was a trend toward a lower rate of response to first-line platinum-based therapy.ConclusionsOur study suggests that CCOC consists of two distinct molecular subclasses with distinct clinical presentation and outcomes, with potential relevance to both traditional and experimental therapy responsiveness. See related commentary by Lheureux, p. 4838.

The study attempts to determine the epidemiologic features of the Zika virus outbreak on Yap Island, Federated States of Micronesia and to also describe the clinical manifestations of the disease. The results indicate that the outbreak represents a transmission of the virus outside Asia and Africa and the need to create public awareness to avoid further expansion of the virus.

To the Editor: We wish to clarify an inaccuracy in a letter in Emerging Infectious Diseases by Cao-Lormeau et al. (1). The authors state 'In 2007, the first ZIKV outbreak [...]

Between May and December 2004,Yap State experienced an outbreak of Dengue Fever, type 1 with a final total of 658 recorded clinically compatible cases, including 42 hospitalisations and 12 cases of dengue haemorrhagic fever/shock syndrome. There were no fatalities. Lessons learned from this outbreak include: the importance maintaining a high index of suspicion and on-site diagnostic capability for dengue fever, the importance of prompt in-service training for health care workers, the danger posed to neighbors by local lapses in outbreak prone disease surveillance and the utility of the Pacific Public Health Surveillance Network in responding to such diseases, the importance of active disease surveillance in outer island populations, and the importance of instituting preventive measures against the nosocomial spread of dengue fever.