Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • IR spectroscopy  (3)
  • ACUTE LYMPHOBLASTIC-LEUKEMIA  (2)
  • LANDSCAPE  (2)
Keywords
Publisher
Years
  • 1
    Keywords: CANCER ; PATHWAY ; GENES ; ACTIVATION ; MUTATIONS ; SUBGROUPS ; LANDSCAPE ; TETRAPLOID TUMOR-CELLS ; TBR1
    Abstract: Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified. WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis. Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patients.
    Type of Publication: Journal article published
    PubMed ID: 22832583
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: PROSTATE-CANCER ; ACUTE LYMPHOBLASTIC-LEUKEMIA ; SQUAMOUS-CELL CARCINOMA ; LUNG ADENOCARCINOMA ; ACUTE MYELOID-LEUKEMIA ; SOMATIC MUTATIONS ; GENETIC LANDSCAPE ; 21 BREAST CANCERS ; RECURRENT MUTATIONS ; FREQUENT MUTATION
    Abstract: All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
    Type of Publication: Journal article published
    PubMed ID: 23945592
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: PATHWAY ; COMPLEX ; leukemia ; CHILDHOOD ; STRUCTURAL BASIS ; cancer genes ; LANDSCAPE
    Abstract: Medulloblastomas are themost commonmalignant brain tumours in children(1). Identifying and understanding the genetic events that drive these tumours is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes ofmedulloblastoma on the basis of transcriptional and copy number profiles(2-5). Here we use whole-exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas have low mutation rates consistent with other paediatric tumours, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 andTP53. Recurrent somatic mutations were newly identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR and LDB1. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant, but not wild-type, beta-catenin. Together, our study reveals the alteration ofWNT, hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates theRNA helicase DDX3X as a component of pathogenic b-catenin signalling in medulloblastoma.
    Type of Publication: Journal article published
    PubMed ID: 22820256
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: COLORECTAL-CANCER ; ACUTE LYMPHOBLASTIC-LEUKEMIA ; STEM-CELLS ; medulloblastoma ; GLIOBLASTOMA ; GENE-EXPRESSION SIGNATURE ; DISTINCT SUBGROUPS ; ISLAND METHYLATOR PHENOTYPE ; DRIVER MUTATIONS ; GENOMIC COMPLEXITY
    Abstract: Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.
    Type of Publication: Journal article published
    PubMed ID: 24553142
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1572-879X
    Keywords: platinum carbonyls ; KL zeolite supported Pt ; CO chemisorption on Pt ; IR spectroscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Reactivity of Pt metal clusters supported on KL zeolite toward CO was studied by FTIR spectroscopy. Investigation of the CO adsorption was performed within a wide CO pressure range (1–500 mbar). IR data on the CO adsorption at high pressure (500 mbar) suggest the transformation of the finest Pt particles into neutral Pt carbonyls ((Zeol-O:) m Pt x (CO) y ) stabilized by the basic oxygen atoms of the KL framework. The transformation is found to be readily reversible upon CO adsorption-desorption at room temperature (RT).
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1572-879X
    Keywords: Pt/KL zeolite ; CO chemisorption on Pt ; IR spectroscopy ; electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Electronic state and location of Pt metal clusters supported on KL zeolite are studied by FTIR spectroscopy of adsorbed CO. Investigation of the CO adsorption was performed within the wide CO pressure range (from 4×10−3 to 102 Pa) and supplemented by the study of the CO desorption at elevated temperature. Comparison of the data on CO adsorption and desorption at increased temperature reveals the existence of two groups of Pt particles in the sample. The first group of the particles is localized on the outer surface of the zeolite microcrystals and in the near surface region; they exhibit CO bands at 2060-2050 cm−1 close to those of Pt supported on conventional supports. The particles of the second group are encaged inside zeolite channels and their electronic structure is presumably strongly perturbed by the zeolite framework. CO adsorbed on the Pt particles of this group exhibits coverage dependent bands at frequencies in the range 1960-1920 cm−1. The marked downward shift of thevCO band is attributed to the increase of electron density on these particles.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1572-879X
    Keywords: anionic Pt-carbonyl complexes ; CO chemisorption on Pt ; IR spectroscopy ; UV/VIS diffuse reflectance spectroscopy ; faujasites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The temporal generation of anionic platinum-carbonyl complexes in platinum ionexchanged zeolites X and Y by reductive carbonylation at 105 Pa and 363 K is monitored by in situ UV/VIS and FTIR spectroscopy. A monomer [Pt3(CO)6]2−, exhibiting bands at 318 and 456 nm in the UV/VIS spectra and at 1790 and 2025 cm−1 in the FTIR spectra, is the only platinum/species formed in NaX. The monomer as well as oligomers are generated in NaY, where the formation of the latter species is due to the stronger acidity in the NaY as compared to NaX. The decomposition of the complexes results in the generation of Pt clusters of the size ≤1 nm.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...