Person:

Lin, William

Somatic alterations in cellular DNA underlie almost all human cancers1. The prospect of targeted therapies2 and the development of high-resolution, genome-wide approaches3–8 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 tumors (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 ~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.

A 25-year-old otherwise healthy male presented with new-onset odynophagia, rash, and orogenital ulcers. Despite treatment with antibiotics for presumed bacterial pharyngitis, the patient remained symptomatic, with abnormal vital signs and laboratory values. Upon dermatology consultation and histopathologic correlation, he was diagnosed with Behçet disease. Behçet disease is a rare rheumatologic condition that presents with recurrent oral ulcers and varying degrees of ophthalmic, neurologic, cardiac, and vascular disease. Given its protean nature, the treatment of Behçet disease is tailored to the patient's presentation and severity of organ involvement. Following treatment with colchicine and prednisone, the patient's symptoms improved rapidly.