Array comparative genomic hybridization-based characterization of genetic alterations in pulmonary neuroendocrine tumors.

Abstract:

:The goal of this study was to characterize and classify pulmonary neuroendocrine tumors based on array comparative genomic hybridization (aCGH). Using aCGH, we performed karyotype analysis of 33 small cell lung cancer (SCLC) tumors, 13 SCLC cell lines, 19 bronchial carcinoids, and 9 gastrointestinal carcinoids. In contrast to the relatively conserved karyotypes of carcinoid tumors, the karyotypes of SCLC tumors and cell lines were highly aberrant. High copy number (CN) gains were detected in SCLC tumors and cell lines in cytogenetic bands encoding JAK2, FGFR1, and MYC family members. In some of those samples, the CN of these genes exceeded 100, suggesting that they could represent driver alterations and potential drug targets in subgroups of SCLC patients. In SCLC tumors, as well as bronchial carcinoids and carcinoids of gastrointestinal origin, recurrent CN alterations were observed in 203 genes, including the RB1 gene and 59 microRNAs of which 51 locate in the DLK1-DIO3 domain. These findings suggest the existence of partially shared CN alterations in these tumor types. In contrast, CN alterations of the TP53 gene and the MYC family members were predominantly observed in SCLC. Furthermore, we demonstrated that the aCGH profile of SCLC cell lines highly resembles that of clinical SCLC specimens. Finally, by analyzing potential drug targets, we provide a genomics-based rationale for targeting the AKT-mTOR and apoptosis pathways in SCLC.

authors

Voortman J,Lee JH,Killian JK,Suuriniemi M,Wang Y,Lucchi M,Smith WI Jr,Meltzer P,Wang Y,Giaccone G

doi

10.1073/pnas.1008132107

subject

Has Abstract

pub_date

2010-07-20 00:00:00

pages

13040-5

issue

29

eissn

0027-8424

issn

1091-6490

pii

1008132107

journal_volume

107

pub_type

杂志文章
  • Targeting a binding pocket within the trimer-of-hairpins: small-molecule inhibition of viral fusion.

    abstract::Trimeric class I virus fusion proteins undergo a series of conformational rearrangements that leads to the association of C- and N-terminal heptad repeat domains in a "trimer-of-hairpins" structure, facilitating the apposition of viral and cellular membranes during fusion. This final fusion hairpin structure is sustai...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0406696101

    authors: Cianci C,Langley DR,Dischino DD,Sun Y,Yu KL,Stanley A,Roach J,Li Z,Dalterio R,Colonno R,Meanwell NA,Krystal M

    更新日期:2004-10-19 00:00:00

  • Beta 3-adrenergic receptor stimulation restores message and expression of brown-fat mitochondrial uncoupling protein in adult dogs.

    abstract::Brown adipose tissue (BAT) is present throughout life in rodents and plays an important role in energy balance. However, whereas BAT is clearly recognizable in the neonates of larger mammals (including dogs, cats, sheep, cattle, and humans), it is undetectable or present in only small quantities in adults of these spe...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.23.10774

    authors: Champigny O,Ricquier D,Blondel O,Mayers RM,Briscoe MG,Holloway BR

    更新日期:1991-12-01 00:00:00

  • ATP-driven Ca2+/H+ antiport in acid vesicles from Dictyostelium.

    abstract::Amoebae of the cellular slime mold Dictyostelium discoideum possess an extensive and dynamic endomembrane system that includes many types of acidic vacuoles. A light membrane fraction from Dictyostelium, rich in vacuolar-type H(+)-ATPase, has been described [Padh, H., Lavasa, M. & Steck, T.L. (1989) J. Cell Biol. 108,...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.17.8025

    authors: Rooney EK,Gross JD

    更新日期:1992-09-01 00:00:00

  • The structure of zetekitoxin AB, a saxitoxin analog from the Panamanian golden frog Atelopus zeteki: a potent sodium-channel blocker.

    abstract::Bufonid anurans of the genus Atelopus contain both steroidal bufadienolides and various guanidinium alkaloids of the tetrodotoxin class. The former inhibit sodium-potassium ATPases, whereas the latter block voltage-dependent sodium channels. The structure of one guanidinium alkaloid, zetekitoxin AB, has remained a mys...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0400368101

    authors: Yotsu-Yamashita M,Kim YH,Dudley SC Jr,Choudhary G,Pfahnl A,Oshima Y,Daly JW

    更新日期:2004-03-30 00:00:00

  • A growing microcolony can survive and support persistent propagation of virulent phages.

    abstract::Bacteria form colonies and secrete extracellular polymeric substances that surround the individual cells. These spatial structures are often associated with collaboration and quorum sensing between the bacteria. Here we investigate the mutual protection provided by spherical growth of a monoclonal colony during exposu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1708954115

    authors: Eriksen RS,Svenningsen SL,Sneppen K,Mitarai N

    更新日期:2018-01-09 00:00:00

  • Discovery and characterization of an epithelial-specific galectin in the endometrium that forms crystals in the trophectoderm.

    abstract::Secretions of the uterus support survival and growth of the conceptus (embryo/fetus and associated membranes) during pregnancy. Galectin-15, also known as OVGAL11 and a previously uncharacterized member of the galectin family of secreted beta-galactoside lectins containing a conserved carbohydrate recognition domain a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0402669101

    authors: Gray CA,Adelson DL,Bazer FW,Burghardt RC,Meeusen EN,Spencer TE

    更新日期:2004-05-25 00:00:00

  • Modulation of rhythmic brain activity by diazepam: GABA(A) receptor subtype and state specificity.

    abstract::The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is involved in the generation of various brain rhythmic activities that can be modulated by benzodiazepines. Here, we assessed the contribution of alpha(2)GABA type A (GABA(A)) receptors to the effects of benzodiazepines on sleep and waking oscillatory pat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0306975101

    authors: Kopp C,Rudolph U,Löw K,Tobler I

    更新日期:2004-03-09 00:00:00

  • Structural basis of sequence-specific collagen recognition by SPARC.

    abstract::Protein interactions with the collagen triple helix play a critical role in collagen fibril formation, cell adhesion, and signaling. However, structural insight into sequence-specific collagen recognition is limited to an integrin-peptide complex. A GVMGFO motif in fibrillar collagens (O denotes 4-hydroxyproline) bind...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0808452105

    authors: Hohenester E,Sasaki T,Giudici C,Farndale RW,Bächinger HP

    更新日期:2008-11-25 00:00:00

  • In vivo natural killer cell activities revealed by natural killer cell-deficient mice.

    abstract::Studies of natural killer (NK) cell function in vivo have been challenging primarily due to the lack of animal models in which NK cells are genetically and selectively deficient. Here, we describe a transgenic mouse with defective natural killing and selective deficiency in NK1.1(+) CD3(-) cells. Despite functionally ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.050588297

    authors: Kim S,Iizuka K,Aguila HL,Weissman IL,Yokoyama WM

    更新日期:2000-03-14 00:00:00

  • Atoms of recognition in human and computer vision.

    abstract::Discovering the visual features and representations used by the brain to recognize objects is a central problem in the study of vision. Recently, neural network models of visual object recognition, including biological and deep network models, have shown remarkable progress and have begun to rival human performance in...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1513198113

    authors: Ullman S,Assif L,Fetaya E,Harari D

    更新日期:2016-03-08 00:00:00

  • Temperature-sensitive mutants of Escherichia coli requiring saturated and unsaturated fatty acids for growth: isolation and properties.

    abstract::A procedure is described for selection of temperature-sensitive mutants affecting fatty-acid synthesis based upon radiation suicide of wild-type organisms by tritiated acetate selectively incorporated into fatty acids. At 37 degrees , two of the mutants extensively incorporate fatty-acid supplements provided in the me...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.11.3105

    authors: Harder ME,Beacham IR,Cronan JE Jr,Beacham K,Honegger JL,Silbert DF

    更新日期:1972-11-01 00:00:00

  • Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex.

    abstract::Reward-guided decision-making depends on a network of brain regions. Among these are the orbitofrontal and the anterior cingulate cortex. However, it is difficult to ascertain if these areas constitute anatomical and functional unities, and how these areas correspond between monkeys and humans. To address these questi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1410767112

    authors: Neubert FX,Mars RB,Sallet J,Rushworth MF

    更新日期:2015-05-19 00:00:00

  • CaV1.2 beta-subunit coordinates CaMKII-triggered cardiomyocyte death and afterdepolarizations.

    abstract::Excessive activation of calmodulin kinase II (CaMKII) causes arrhythmias and heart failure, but the cellular mechanisms for CaMKII-targeted proteins causing disordered cell membrane excitability and myocardial dysfunction remain uncertain. Failing human cardiomyocytes exhibit increased CaMKII and voltage-gated Ca(2+) ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0913760107

    authors: Koval OM,Guan X,Wu Y,Joiner ML,Gao Z,Chen B,Grumbach IM,Luczak ED,Colbran RJ,Song LS,Hund TJ,Mohler PJ,Anderson ME

    更新日期:2010-03-16 00:00:00

  • Mammalian monogamy is not controlled by a single gene.

    abstract::Complex social behavior in Microtus voles and other mammals has been postulated to be under the direct genetic control of a single locus: the arginine vasopressin 1a receptor (avpr1a) gene. Using a phylogenetic approach, we show that a repetitive element in the promoter region of avpr1a, which reportedly causes social...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0602380103

    authors: Fink S,Excoffier L,Heckel G

    更新日期:2006-07-18 00:00:00

  • Elongation of displacement-loop strands in human and mouse mitochondrial DNA is arrested near specific template sequences.

    abstract::Animal mitochondrial DNA (mtDNA) maintains a displacement loop (D loop) at the heavy strand origin of replication. These D loops represent sharply limited synthesis of heavy strands and provide a unique opportunity to examine the termination of DNA synthesis. Direct sizing at the nucleotide level indicates that the 3'...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.10.6116

    authors: Doda JN,Wright CT,Clayton DA

    更新日期:1981-10-01 00:00:00

  • Stabilization of electron spin resonance probes for photosynthesis studies.

    abstract::The major obstacle to the study of functional/structural interrelationships of spinach chloroplasts by using spin labels has been the rapid loss of the electron paramagnetic resonance (EPR) signals upon illumination with visible light. The present study demonstrates that the addition of ferredoxin and NADP+ in the pre...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.8.3107

    authors: Sun AS,Calvin M

    更新日期:1975-08-01 00:00:00

  • On the Fundamental Group of Manifolds of Non-positive Curvature.

    abstract::We prove theorems on the structure of the fundamental group of a compact riemannian manifold of non-positive curvature. In particular, a conjecture of J. Wolf [J. Differential Geometry, 2, 421-446 (1968)] is proved. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.67.2.509

    authors: Yau ST

    更新日期:1970-10-01 00:00:00

  • Rotational dynamics of DNA on the nucleosome surface markedly impact accessibility to a DNA repair enzyme.

    abstract::Histones play a crucial role in the organization of DNA in the nucleus, but their presence can prevent interactions with DNA binding proteins responsible for repair of DNA damage. Uracil is an abundant mutagenic lesion recognized by uracil DNA glycosylase (UDG) in the first step of base excision repair (BER). In nucle...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0914443107

    authors: Hinz JM,Rodriguez Y,Smerdon MJ

    更新日期:2010-03-09 00:00:00

  • Reconstitution of functional receptors for human granulocyte/macrophage colony-stimulating factor (GM-CSF): evidence that the protein encoded by the AIC2B cDNA is a subunit of the murine GM-CSF receptor.

    abstract::The high-affinity receptor for human granulocyte/macrophage colony-stimulating factor (hGM-CSF) is composed of two subunits, alpha and beta. The alpha subunit binds GM-CSF with low affinity, whereas the beta subunit does not bind GM-CSF by itself. The alpha and beta subunits together form the high-affinity GM-CSF rece...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.12.5082

    authors: Kitamura T,Hayashida K,Sakamaki K,Yokota T,Arai K,Miyajima A

    更新日期:1991-06-15 00:00:00

  • Growth-and density-dependent inhibition of deoxyglucose transport in Balb 3T3 cells and its absence in cells transformed by murine sarcoma virus.

    abstract::The earliest measurable parameter that shows density-dependent inhibition is the uptake of [(3)H]deoxyglucose by Balb 3T3 cells. The rate decreases even during the exponential phase of growth and reaches a minimum, about 8- to 10-times lower than maximum, as the culture approaches the saturation density. Cells transfo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.70.8.2374

    authors: Bose SK,Zlotnick BJ

    更新日期:1973-08-01 00:00:00

  • Proteolytic maturation of protein C upon engineering the mouse mammary gland to express furin.

    abstract::Endoproteolytic processing of the human protein C (HPC) precursor to its mature form involves cleavage of the propeptide after amino acids Lys-2-Arg-1 and removal of a Lys156-Arg157 dipeptide connecting the light and heavy chains. This processing was inefficient in the mammary gland of transgenic mice and pigs. We hyp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.23.10462

    authors: Drews R,Paleyanda RK,Lee TK,Chang RR,Rehemtulla A,Kaufman RJ,Drohan WN,Luboń H

    更新日期:1995-11-07 00:00:00

  • A glycopeptide in complex with MHC class I uses the GalNAc residue as an anchor.

    abstract::Peptides bind MHC class I molecules by anchoring hydrophobic side chains into pockets in the peptide binding groove. Here, we report an immunogenic (in vitro and in vivo) MUC1 glycopeptide (MUC1-8-5GalNAc) bound to H-2Kb, fully crossreactive with the nonglycosylated variant. Molecular modeling showed that the central ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2432220100

    authors: Apostolopoulos V,Yuriev E,Ramsland PA,Halton J,Osinski C,Li W,Plebanski M,Paulsen H,McKenzie IF

    更新日期:2003-12-09 00:00:00

  • Cation-dependent mannose 6-phosphate receptor contains two internalization signals in its cytoplasmic domain.

    abstract::The signals required for rapid internalization of the bovine cation-dependent mannose 6-phosphate receptor have been localized to two distinct regions of the 67-amino acid cytoplasmic domain. One signal includes phenylalanine 13 and phenylalanine 18, while the other involves tyrosine 45. The former signal is more pote...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.24.10010

    authors: Johnson KF,Chan W,Kornfeld S

    更新日期:1990-12-01 00:00:00

  • Emergent perversions in the buckling of heterogeneous elastic strips.

    abstract::A perversion in an otherwise uniform helical structure, such as a climbing plant tendril, refers to a kink that connects two helices with opposite chiralities. Such singularity structures are widely seen in natural and artificial mechanical systems, and they provide the fundamental mechanism of helical symmetry breaki...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1605621113

    authors: Liu S,Yao Z,Chiou K,Stupp SI,Olvera de la Cruz M

    更新日期:2016-06-28 00:00:00

  • Diel variability of methane emissions from lakes.

    abstract::Lakes are considered the second largest natural source of atmospheric methane (CH4). However, current estimates are still uncertain and do not account for diel variability of CH4 emissions. In this study, we performed high-resolution measurements of CH4 flux from several lakes, using an automated and sensor-based flux...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2006024117

    authors: Sieczko AK,Duc NT,Schenk J,Pajala G,Rudberg D,Sawakuchi HO,Bastviken D

    更新日期:2020-09-01 00:00:00

  • Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa.

    abstract::Opportunistic infections are often polymicrobial. Two of the most important bacterial opportunistic pathogens of humans, Pseudomonas aeruginosa and Staphylococcus aureus, frequently are coisolated from infections of catheters, endotracheal tubes, skin, eyes, and the respiratory tract, including the airways of people w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0606756104

    authors: Hoffman LR,Déziel E,D'Argenio DA,Lépine F,Emerson J,McNamara S,Gibson RL,Ramsey BW,Miller SI

    更新日期:2006-12-26 00:00:00

  • Role of gender, season, and familiarity in discrimination of conspecific song by zebra finches (Taeniopygia guttata).

    abstract::Operant conditioning techniques were used to assess how gender and song familiarity affect song discrimination in adult zebra finches (Taeniopygia guttata). Twenty-five males and females, divided into five cohorts, were trained to discriminate between conspecific songs at different times of year. Males discriminating ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.4.1368

    authors: Cynx J,Nottebohm F

    更新日期:1992-02-15 00:00:00

  • Localization of calmodulin in rat tissues.

    abstract::The localization of calmodulin, a calcium-dependent modulator of many enzymes, was studied in rat liver, skeletal muscle, and adrenal slices. Calmodulin is found in liver cytoplasm, nucleus, and plasma membrane. Much of the cytoplasmic calmodulin is associated with glycogen particles presumably bound to enzymes involv...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.1.366

    authors: Harper JF,Cheung WY,Wallace RW,Huang HL,Levine SN,Steiner AL

    更新日期:1980-01-01 00:00:00

  • Cluster-like coordinates in supersymmetric quantum field theory.

    abstract::Recently it has become apparent that N = 2 supersymmetric quantum field theory has something to do with cluster algebras. I review one aspect of the connection: supersymmetric quantum field theories have associated hyperkähler moduli spaces, and these moduli spaces carry a structure that looks like an extension of the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1313073111

    authors: Neitzke A

    更新日期:2014-07-08 00:00:00

  • Quality control of ribosomal RNA mediated by polynucleotide phosphorylase and RNase R.

    abstract::Despite their overall accuracy, errors in macromolecular processes, such as rRNA synthesis and ribosome assembly, inevitably occur. However, whether these errors are remediated and how this might be accomplished is not known. In previous work, we showed that a double mutant strain lacking both polynucleotide phosphory...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1231041100

    authors: Cheng ZF,Deutscher MP

    更新日期:2003-05-27 00:00:00