SHRIMP ion probe zircon geochronology and Sr and Nd isotope geochemistry for southern Longwood Range and Bluff Peninsula intrusive rocks of Southland, New Zealand

Permian–Jurassic ultramafic to felsic intrusive complexes at Bluff Peninsula and in the southern Longwood Range along the Southland coast represent a series of intraoceanic magmatic arcs with ages spanning a time interval of 110 m.y. New SHRIMP U-Pb zircon data for a quartz diorite from the Flat Hill complex, Bluff Peninsula, yield an age of 259 ± 4 Ma, consistent with other geochronological and paleontological evidence confirming a Late Permian age. The new data are consistent with an age of c. 260 Ma for the intrusive rocks of the Brook Street Terrane. SHRIMP U-Pb zircon ages for the southern Longwood Range confirm that intrusions become progressively younger from east to west across the complex. A gabbro at Oraka Point (eastern end of coastal section) has an age of 245 ± 4 Ma and shows virtually no evidence of zircon inheritance. The age is significantly different from that of the Brook Street Terrane intrusives. Zircon ages from the western parts of the section are younger and more varied (203–227 Ma), indicating more complex magmatic histories. A leucogabbro dike from Pahia Point gives the youngest emplacement age of 142 Ma, which is similar to published U-Pb zircon ages for the Anglem Complex and Paterson Group on Stewart Island

Genome-scale screen for DNA methylation-based detection markers for ovarian cancer.

The identification of sensitive biomarkers for the detection of ovarian cancer is of high clinical relevance for early detection and/or monitoring of disease recurrence. We developed a systematic multi-step biomarker discovery and verification strategy to identify candidate DNA methylation markers for the blood-based detection of ovarian cancer

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Disorders of Microtubule Function in Neurons: Imaging Correlates

Background and purposeA number of recent studies have described malformations of cortical development with mutations of components of microtubules and microtubule-associated proteins. Despite examinations of a large number of MRIs, good phenotype-genotype correlations have been elusive. Additionally, most of these studies focused exclusively on cerebral cortical findings. The purpose of this study was to characterize imaging findings associated with disorders of microtubule function.Materials and methodsMRIs from 18 patients with confirmed tubulin mutations (8 TUBA1A, 5 TUBB2B, and 5 TUBB3) and 15 patients with known mutations of the genes encoding microtubule-associated proteins (5 LIS1, 4 DCX, and 6 DYNC1H1) were carefully visually analyzed and compared. Specific note was made of the cortical gyral pattern, basal ganglia, and white matter to assess internal capsular size, cortical thickness, ventricular and cisternal size, and the size and contours of the brain stem, cerebellar hemispheres and vermis, and the corpus callosum of patients with tubulin and microtubule-associated protein gene mutations. Results were determined by unanimous consensus of the authors.ResultsAll patients had abnormal findings on MR imaging. A large number of patients with tubulin gene mutations were found to have multiple cortical and subcortical abnormalities, including microcephaly, ventriculomegaly, abnormal gyral and sulcal patterns (termed "dysgyria"), a small or absent corpus callosum, and a small pons. All patients with microtubule-associated protein mutations also had abnormal cerebral cortices (predominantly pachygyria and agyria), but fewer subcortical abnormalities were noted.ConclusionsComparison of MRIs from patients with known mutations of tubulin genes and microtubule-associated proteins allows the establishment of some early correlations of phenotype with genotype and may assist in identification and diagnosis of these rare disorders