Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence.

Amplifications at 9p24 have been identified in breast cancer and other malignancies, but the genes within this locus causally associated with oncogenicity or tumor progression remain unclear. Targeted next-generation sequencing of postchemotherapy triple-negative breast cancers (TNBCs) identified a group of 9p24-amplified tumors, which contained focal amplification of the Janus kinase 2 (JAK2) gene. These patients had markedly inferior recurrence-free and overall survival compared to patients with TNBC without JAK2 amplification.

Loss of antigenicity with tissue age in breast cancer.

Archived tumor specimens, particularly those collected by large cooperative groups and trials, provide a wealth of material for post hoc clinical investigation. As these tissues are rigorously collected and preserved for many decades, subsequent use of the specimens to answer clinical questions must rely on the assumption that expression and detection of target biomarkers are not degraded with time. To test this assumption, we measured the expression of estrogen receptor (ER), human epidermal growth receptor 2 (HER2), and Ki67 in human breast carcinoma using quantitative immunofluorescence (QIF) in a series of formalin-fixed paraffin-embedded (FFPE) tissues from 1295 individual patients preserved for 7 to 53 years in four cohorts on tissue microarrays.

Bolstering the case for lobectomy in stages I, II, and IIIA small-cell lung cancer using the National Cancer Data Base.

Introduction: Current therapy for small-cell lung cancer (SCLC) relies on chemoradiation therapy, and the role of primary surgical resection in these patients remains controversial. A minority of SCLC patients present without metastatic disease and are candidates for surgery. This study investigates the role of surgical resection in select patients with SCLC, using a national cohort of approximately 2500 resected patients.

Assessment of genetics knowledge and skills in medical students: insight for a clinical neurogenetics curriculum.

The pace of discovery in biochemistry and genetics and its effect on clinical medicine places new curricular challenges in medical school education. We sought to evaluate students' understanding of neurogenetics and its clinical applications to design a pilot curriculum into the clinical neurology clerkship. We utilized a needs assessment and a written examination to evaluate the genetics knowledge of 81 third- and fourth-year medical students.

Polysomnographic abnormalities in succinic semialdehyde dehydrogenase (SSADH) deficiency.

Objectives: Patients with SSADH deficiency, a disorder of chronically elevated endogenous GABA and GHB, were studied for sleep symptoms and polysomnography. We hypothesized that patients would have excessive daytime somnolence and decreased REM sleep.

Design: Polysomnography and MSLT were performed on patients enrolled for comprehensive clinical studies of SSADH deficiency.

The structure and transcriptional analysis of a global regulator from Neisseria meningitidis.

Neisseria meningitidis, a causative agent of bacterial meningitis, has a relatively small repertoire of transcription factors, including NMB0573 (annotated AsnC), a member of the Lrp-AsnC family of regulators that are widely expressed in both Bacteria and Archaea. In the present study we show that NMB0573 binds to l-leucine and l-methionine and have solved the structure of the protein with and without bound amino acids. This has shown, for the first time that amino acid binding does not induce significant conformational changes in the structure of an AsnC/Lrp regulator although it does appear to stabilize the octameric assembly of the protein.