Phylogeny of Agavaceae Based on ndhF, rbcL, and its Sequences

Great advances have been made in our understanding of the phylogeny and classification of Agavaceae in the last 20 years. In older systems Agavaceae were paraphyletic due to overemphasis of ovary position or habit. Discovery of a unique bimodal karyotype in Agave and Yucca eventually led to a reexamination of concepts and relationships in all the lilioid monocots, which continues to the present day. Developments in cytogenetics, microscopy, phylogenetic systematics, and most recently DNA technology have led to remarkable new insights. Large-scale rbcL sequence studies placed Agavaceae with the core Asparagales and identified closely related taxa. Analysis of cpDNA restriction sites, rbcL, and ITS nrDNA sequences all supported removal of Dracaenaceae, Nolinaceae, and clarified relationships. Agavaceae s.s. presently consists of Agave, Beschorneria, Furcraea, Hesperaloe, Hesperoyucca, Manfreda, Polianthes, Prochnyanthes, and Yucca. In this paper we analyze recently obtained ndhF sequence data from Agavaceae and Asparagales and discuss the implications for classification. Parsimony analysis of ndhF data alone resolves most genera of Agavaceae and supports the inclusion of Camassia, Chlorogalum, Hesperocallis, and Hosta within Agavaceae s.l. Analysis of combined ndhF and rbcL data sets of selected Asparagales results in better resolution and stronger bootstrap support for many relationships. Combination of all available ndhF, rbcL, and ITS data in a single analysis results in the best resolution currently available for Agavaceae s.l. Implications for classification schemes past and present are discussed

Optical Propagation and Communication

Contains reports on four research projects.National Science Foundation (Grant ENG78-21603)U.S. Army Research Office - Durham (Contract DAAG29-80-K-0022)U.S. Navy - Office of Naval Research (Contract N00014-81-K-0662)U.S. Navy - Office of Naval Research (Contract N00014-80-C-0941

Optical Propagation and Communication

Contains research objectives and reports on five research projects.National Science Foundation (Grant ECS81-20637)U.S. Army Research Office - Durham (Contract DAAG29-80-K-0022)U.S. Navy - Office of Naval Research (Contract N00014-81-K-0662)U.S. Navy - Office of Naval Research (Contract N00014-80-C-0941

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal canceropen40

Comprehensive genomic characterization defines human glioblastoma genes and core pathways

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas ( TCGA) pilot project aims to assess the value of large- scale multi- dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of primary adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol- 3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer