Characterizing the cancer genome in lung adenocarcinoma

Somatic alterations in cellular DNA underlie almost all human cancers(1). The prospect of targeted therapies(2) and the development of high-resolution, genome-wide approaches(3-8) are now spurring systematic efforts to characterize cancer genomes. Here we report a large-scale project to characterize copy-number alterations in primary lung adenocarcinomas. By analysis of a large collection of tumours ( n = 371) using dense single nucleotide polymorphism arrays, we identify a total of 57 significantly recurrent events. We find that 26 of 39 autosomal chromosome arms show consistent large-scale copy-number gain or loss, of which only a handful have been linked to a specific gene. We also identify 31 recurrent focal events, including 24 amplifications and 7 homozygous deletions. Only six of these focal events are currently associated with known mutations in lung carcinomas. The most common event, amplification of chromosome 14q13.3, is found in similar to 12% of samples. On the basis of genomic and functional analyses, we identify NKX2-1 ( NK2 homeobox 1, also called TITF1), which lies in the minimal 14q13.3 amplification interval and encodes a lineage-specific transcription factor, as a novel candidate proto-oncogene involved in a significant fraction of lung adenocarcinomas. More generally, our results indicate that many of the genes that are involved in lung adenocarcinoma remain to be discovered.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62944/1/nature06358.pd

Performance of the Pediatric Glasgow Coma Scale Score in the Evaluation of Children With Blunt Head Trauma

ObjectiveThe objective was to compare the accuracy of the pediatric Glasgow Coma Scale (GCS) score in preverbal children to the standard GCS score in older children for identifying those with traumatic brain injuries (TBIs) after blunt head trauma.MethodsThis was a planned secondary analysis of a large prospective observational multicenter cohort study of children with blunt head trauma. Clinical data were recorded onto case report forms before computed tomography (CT) results or clinical outcomes were known. The total and component GCS scores were assigned by the physician at initial emergency department evaluation. The pediatric GCS was used for children <2 years old and the standard GCS for those ≥2 years old. Outcomes were TBI visible on CT and clinically important TBI (ciTBI), defined as death from TBI, neurosurgery, intubation for more than 24 hours for the head injury, or hospitalization for 2 or more nights for the head injury in association with TBI on CT. We compared the areas under the receiver operating characteristic (ROC) curves between age cohorts for the association of GCS and the TBI outcomes.ResultsWe enrolled 42,041 patients, of whom 10,499 (25.0%) were <2 years old. Among patients <2 years, 313/3,329 (9.4%, 95% confidence interval [CI] = 8.4% to 10.4%) of those imaged had TBIs on CT and 146/10,499 (1.4%, 95% CI = 1.2% to 1.6%) had ciTBIs. In patients ≥2 years, 773/11,977 (6.5%, 95% CI = 6.0% to 6.9%) of those imaged had TBIs on CT and 572/31,542 (1.8%, 95% CI = 1.7% to 2.0%) had ciTBIs. For the pediatric GCS in children <2 years old, the area under the ROC curve was 0.61 (95% CI = 0.59 to 0.64) for TBI on CT and 0.77 (95% CI = 0.73 to 0.81) for ciTBI. For the standard GCS in older children, the area under the ROC curve was 0.71 (95% CI = 0.70 to 0.73) for TBI on CT scan and 0.81 (95% CI = 0.79 to 0.83) for ciTBI.ConclusionsThe pediatric GCS for preverbal children was somewhat less accurate than the standard GCS for older children in identifying those with TBI on CT. However, the pediatric GCS for preverbal children and the standard GCS for older children were equally accurate for identifying ciTBI.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133544/1/acem13014_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133544/2/acem13014.pd