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Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
BACKGROUND - Although rotavirus and norovirus cause nearly 40% of severe endemic acute gastroenteritis (AGE) in children <5 years of age in the United States, there are limited data on the etiologic role of other enteric viruses in this age group.
METHODS - We conducted active population-based surveillance in children presenting with AGE to hospitals, emergency departments, and primary care clinics in 3 US counties. Stool specimens from these children and from age-matched healthy controls collected between October 2008 and September 2009 were tested for enteric adenovirus, astrovirus, sapovirus, parechovirus, bocavirus, and aichivirus. Typing was performed by sequencing and phylogenetic analysis.
RESULTS - Adenovirus, astrovirus, sapovirus, parechovirus, bocavirus, and aichivirus were detected in the stool specimens of 11.8%, 4.9%, 5.4%, 4.8%, 1.4%, and 0.2% of patients with AGE and 1.8%, 3.0%, 4.2%, 4.4%, 2.4%, and 0% of healthy controls, respectively. Adenovirus (type 41), astrovirus (types 1, 2, 3, 4, and 8), sapovirus (genogroups I and II), parechovirus (types 1, 3, 4, and 5), and bocavirus (types 1, 2, and 3) were found cocirculating.
CONCLUSIONS - Adenovirus, astrovirus, and sapovirus infections were detected in 22.1% of the specimens from children <5 years of age who had medical visits for AGE and tested negative for rotavirus and norovirus. No causal role for parechovirus and bocavirus was found.
OBJECTIVE - To define the molecular epidemiology of colonization and disease-associated isolates of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA).
DESIGN - Laboratory-based comparative study of clinical staphylococcal isolates.
METHODS - We analyzed 255 pediatric CA-MRSA isolates for molecular characteristics associated with colonization and disease. We used polymerase chain reaction to determine the presence of Panton-Valentine Leukocidin and the lantibiotic element, bsaB, and to characterize the staphylococcal cassette chromosome mec type and accessory gene regulator locus. Pulsed-field gel electrophoresis was used to determine genetic relatedness between strains.
RESULTS - A total of 150 isolates were obtained from patients with clinical disease (37 invasive infections, 113 noninvasive infections) and 105 from subjects with nasal colonization alone. Of 150 disease-associated isolates, 123 (82%) belonged to pulsed-field gel electrophoresis group USA300, whereas only 19 (18%) of 105 colonization isolates were of the USA300 lineage. Colonization isolates were less likely to possess staphylococcal cassette chromosome mec type IV, Panton-Valentine Leukocidin, or agr type 1 (P < 0.001).
CONCLUSIONS - Colonization strains of CA-MRSA in children differ significantly from those strains recovered from patients with staphylococcal infections. This suggests that only colonization with specific strain types, rather than methicillin-resistant Staphylococcus aureus colonization in general, increases the risk for CA-MRSA disease.