| 1. |
- Weinstein, John N., et al.
(author)
-
The cancer genome atlas pan-cancer analysis project
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
-
Research review (peer-reviewed)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
|
|
| 2. |
- Hudson, Thomas J., et al.
(author)
-
International network of cancer genome projects
- 2010
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
-
Journal article (peer-reviewed)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
|
|
| 3. |
- Kuchenbauer, Florian, et al.
(author)
-
Comprehensive analysis of mammalian miRNA* species and their role in myeloid cells.
- 2011
-
In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 118:12, s. 3350-8
-
Journal article (peer-reviewed)abstract
- Processing of pre-miRNA through Dicer1 generates an miRNA duplex that consists of an miRNA and miRNA* strand. Despite the general view that miRNA*s have no functional role, we further investigated miRNA* species in 10 deep-sequencing libraries from mouse and human tissue. Comparisons of miRNA/miRNA* ratios across the miRNA sequence libraries revealed that 50% of the investigated miRNA duplexes exhibited a highly dominant strand. Conversely, 10% of miRNA duplexes showed a comparable expression of both strands, whereas the remaining 40% exhibited variable ratios across the examined libraries, as exemplified by miR-223/miR-223* in murine and human cell lines. Functional analyses revealed a regulatory role for miR-223* in myeloid progenitor cells, which implies an active role for both arms of the miR-223 duplex. This was further underscored by the demonstration that miR-223 and miR-223* targeted the insulin-like growth factor 1 receptor/phosphatidylinositol 3-kinase axis and that high miR-223* levels were associated with increased overall survival in patients with acute myeloid leukemia. Thus, we found a supporting role for miR-223* in differentiating myeloid cells in normal and leukemic cell states. The fact that the miR-223 duplex acts through both arms extends the complexity of miRNA-directed gene regulation of this myeloid key miRNA.
|
|
| 4. |
- Chand, Damini, 1986, et al.
(author)
-
Cell culture and Drosophila model systems define three classes of anaplastic lymphoma kinase mutations in neuroblastoma.
- 2013
-
In: Disease models & mechanisms. - Cambridge, UK : The Company of Biologists. - 1754-8411 .- 1754-8403. ; 6:2, s. 373-82
-
Journal article (peer-reviewed)abstract
- Neuroblastoma is a childhood extracranial solid tumor which is associated with a number of genetic changes. Included in these genetic alterations are mutations in the kinase domain of the Anaplastic Lymphoma Kinase (ALK) receptor tyrosine kinase (RTK), which have been found in both somatic and familial neuroblastoma. In order to treat patients accordingly required characterisation of these mutations in terms of their response to ALK tyrosine kinase inhibitors (TKIs). Here, we report the identification and characterisation of two novel neuroblastoma ALK mutations (A1099T and 1464STOP) which we have investigated together with several previously reported but uncharacterised ALK mutations (T1087I, D1091N, T1151M, M1166R, F1174I and A1234T). In order to understand the potential role of these ALK mutations in neuroblastoma progression we have employed cell culture based systems together with the model organism Drosophila as a readout for ligand-independent activity. Mutation of ALK at position F1174I generates a gain-of-function receptor capable of activating intracellular targets, such as ERK (extracellular signal regulated kinase) and STAT3 (signal transducer and activator of transcription 3) in a ligand independent manner. Analysis of these previously uncharacterised ALK mutants and comparison with ALK(F1174) mutants suggests that ALK mutations observed in neuroblastoma fall into three classes. These are: (i) gain-of-function ligand independent mutations such as ALK(F1174), (ii) kinase-dead ALK mutants, e.g. ALK(I1250T)(Schonherr et al 2011a) or (iii) ALK mutations which are ligand-dependent in nature. Irrespective of the nature of the observed ALK mutants, in every case the activity of the mutant ALK receptors could be abrogated by the ALK inhibitor crizotinib (PF-02341066, Xalkori), albeit with differing levels of sensitivity.
|
|
| 5. |
- Sacchetto, Daniela, et al.
(author)
-
Mammographic density : Comparison of visual assessment with fully automatic calculation on a multivendor dataset
- 2016
-
In: European Radiology. - : Springer. - 0938-7994 .- 1432-1084. ; 26:1, s. 175-183
-
Journal article (peer-reviewed)abstract
- To compare breast density (BD) assessment provided by an automated BD evaluator (ABDE) with that provided by a panel of experienced breast radiologists, on a multivendor dataset. Twenty-one radiologists assessed 613 screening/diagnostic digital mammograms from nine centers and six different vendors, using the BI-RADS a, b, c, and d density classification. The same mammograms were also evaluated by an ABDE providing the ratio between fibroglandular and total breast area on a continuous scale and, automatically, the BI-RADS score. A panel majority report (PMR) was used as reference standard. Agreement (kappa) and accuracy (proportion of cases correctly classified) were calculated for binary (BI-RADS a-b versus c-d) and 4-class classification. While the agreement of individual radiologists with the PMR ranged from kappa = 0.483 to kappa = 0.885, the ABDE correctly classified 563/613 mammograms (92 %). A substantial agreement for binary classification was found for individual reader pairs (kappa = 0.620, standard deviation [SD] = 0.140), individual versus PMR (kappa = 0.736, SD = 0.117), and individual versus ABDE (kappa = 0.674, SD = 0.095). Agreement between ABDE and PMR was almost perfect (kappa = 0.831). The ABDE showed an almost perfect agreement with a 21-radiologist panel in binary BD classification on a multivendor dataset, earning a chance as a reproducible alternative to visual evaluation. aEuro cent Individual BD assessment differs from PMR with kappa as low as 0.483. aEuro cent An ABDE correctly classified 92 % of mammograms with almost perfect agreement (kappa = 0.831). aEuro cent An ABDE can be a valid alternative to subjective BD assessment.
|
|
