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  • 1
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    Sex differences in oncogenic mutational processes
    Springer Science and Business Media LLC ; 2020
    In:  Nature Communications Vol. 11, No. 1 ( 2020-08-28)
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    In: Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-08-28)
    Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-020-17359-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2553671-0
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  • 2
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    Pathway and network analysis of more than 2500 whole cancer genomes
    Springer Science and Business Media LLC ; 2020
    In:  Nature Communications Vol. 11, No. 1 ( 2020-02-05)
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    In: Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-02-05)
    Abstract: The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53 , TLE4 , and TCF4 . We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-020-14367-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2553671-0
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  • 3
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    A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns
    Springer Science and Business Media LLC ; 2020
    In:  Nature Communications Vol. 11, No. 1 ( 2020-02-05)
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    In: Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-02-05)
    Abstract: In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium , we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-019-13825-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2553671-0
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  • 4
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    Foretinib Is Effective Therapy for Metastatic Sonic Hedgehog Medulloblastoma
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 1 ( 2015-01-01), p. 134-146
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    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 1 ( 2015-01-01), p. 134-146
    Abstract: Medulloblastoma is the most common malignant pediatric brain tumor, with metastases present at diagnosis conferring a poor prognosis. Mechanisms of dissemination are poorly understood and metastatic lesions are genetically divergent from the matched primary tumor. Effective and less toxic therapies that target both compartments have yet to be identified. Here, we report that the analysis of several large nonoverlapping cohorts of patients with medulloblastoma reveals MET kinase as a marker of sonic hedgehog (SHH)–driven medulloblastoma. Immunohistochemical analysis of phosphorylated, active MET kinase in an independent patient cohort confirmed its correlation with increased tumor relapse and poor survival, suggesting that patients with SHH medulloblastoma may benefit from MET-targeted therapy. In support of this hypothesis, we found that the approved MET inhibitor foretinib could suppress MET activation, decrease tumor cell proliferation, and induce apoptosis in SHH medulloblastomas in vitro and in vivo. Foretinib penetrated the blood–brain barrier and was effective in both the primary and metastatic tumor compartments. In established mouse xenograft or transgenic models of metastatic SHH medulloblastoma, foretinib administration reduced the growth of the primary tumor, decreased the incidence of metastases, and increased host survival. Taken together, our results provide a strong rationale to clinically evaluate foretinib as an effective therapy for patients with SHH-driven medulloblastoma. Cancer Res; 75(1); 134–46. ©2014 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-13-3629
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
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    PTPS-11ATYPICAL TERATOID/RHABDOID TUMOUR IS AN EPIGENETICALLY HETEROGENEOUS DISEASE CHARACTERIZED BY SUBGROUP SPECIFIC SUPER-ENHANCERS
    Oxford University Press (OUP) ; 2015
    In:  Neuro-Oncology Vol. 17, No. suppl 5 ( 2015-11), p. v181.2-v181
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 17, No. suppl 5 ( 2015-11), p. v181.2-v181
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/nov228.11
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 2094060-9
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  • 6
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    Abstract 3089: (Epi)genetic profiling enables molecular re-classification of CNS-primitive neuroectodermal tumors
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. 3089-3089
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 3089-3089
    Abstract: According to the current WHO classification of CNS tumors, childhood CNS primitive neuro-ectodermal tumors (CNS-PNETs; WHO °IV) are poorly differentiated embryonal tumors with early onset and aggressive clinical behavior. Histological diagnosis can be complicated by morphological heterogeneity and divergent differentiation. Recent studies suggest the existence of molecular subgroups of CNS-PNETs sharing biological characteristics with other childhood CNS tumors. Here, we aimed at a comprehensive molecular characterization of CNS-PNETs and compared our results to profiles of other brain tumor classes in order to define the biological nature of tumors diagnosed as CNS-PNETs. A collective of 197 fresh-frozen or paraffin-embedded tumor samples with an institutional diagnosis “CNS-PNET” was profiled for genome-wide DNA methylation patterns and copy-number alterations, complemented by transcriptomic profiling of a subset (n=63). (Epi-)genetic profiles of CNS-PNETs were compared to those of & gt;1.000 other childhood brain tumors including embryonal, astrocytic, and ependymal entities, and their respective molecular subgroups. We screened selected groups of tumors for recurrent mutations and expression of established molecular markers. Five experienced neuropathologists independently revisited the histology of 48 CNS-PNETs. Bioinformatic analysis of DNA methylation and gene expression profiles using clustering methods and class prediction algorithms resulted in a clear segregation of pediatric brain tumors by histological entities and molecular subgroups. Exceptionally, profiles of tumors classified as “CNS-PNET” suggested significant overlap with various well-defined entities, including AT/RT, ETMR, high-grade glioma, medulloblastoma, and ependymoma. When screening CNS-PNETs with DNA methylation profiles highly resembling other entities, hallmark genetic alterations of these, such as amplification of 19q13.42, mutations in IDH1 or H3F3A, or mutations/deletions of the SMARCB1 locus, were frequently detected. Molecularly distinct tumor subsets were associated with differential protein expression patterns of previously established subgroup markers INI-1, LIN28A, and OLIG2. Blinded histopathological evaluation resulted in a large proportion of CNS-PNETs being re-classified in line with affiliations suggested by molecular diagnostic tools. The correct classification of CNS-PNET remains challenging. Based on the detection of recurrent genetic aberrations, many cases can be reliably re-classified, indicating that a significant proportion of CNS-PNETs may comprise a variety of other tumor subtypes. These findings suggest that the use of established and novel subgroups markers is needed in order to assist the histopathological evaluation of these tumors. The molecular biology underlying distinct subsets of CNS-PNETs only remains to be elucidated. Citation Format: Dominik Sturm, Paul A. Northcott, David T.W. Jones, Andrey Korshunov, Daniel Picard, Peter Lichter, Annie Huang, Stefan M. Pfister, Marcel Kool. (Epi)genetic profiling enables molecular re-classification of CNS-primitive neuroectodermal tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3089. doi:10.1158/1538-7445.AM2014-3089
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2014-3089
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 7
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    Abstract 5050: KCNJ2 constitutes a marker and therapeutic target of high-risk medulloblastomas.
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 5050-5050
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 5050-5050
    Abstract: Medulloblastoma comprises the most common malignant brain tumor in children. Non-WNT/SHH tumors define the most refractory medulloblastoma subgroups. Interestingly, 17q gain, the most common genetic aberration in medulloblastoma, comprises a cytogenetic hallmark of these molecular high-risk tumors detected in group 3 (62%), and group 4 (73%). The majority of recurrent tumors harbor 17q gain in the corresponding primary. Virtually all of these tumors develop resistance to current treatment protocols at relapse. The lack of a common molecular target hampers the development of urgently needed novel treatment strategies. Through mRNA expression profiling of 64 primary tumor samples, we identified potassium inwardly-rectifying channel J2 (KCNJ2) as one of the most upregulated genes on chromosome 17q in tumors with 17q gain. High KCNJ2 transcript levels were significantly associated with non-WNT/non-SHH grouping, anaplastic histology, metastatic dissemination, and poor clinical outcome. KCNJ2 protein expression was analyzed by immunohistochemistry in a large cohort of patients (n=199), and high protein expression levels were found to be strongly correlated with 17q gain, metastatic dissemination, and inferior prognosis (p & lt;0.0001). To functionally validate the potential role of KCNJ2 in medulloblastoma biology, we performed knockdown experiments by small interfering RNA-mediated silencing in two well-characterized medulloblastoma cell lines. Transient knockdown of KCNJ2 resulted in a reduced proliferation rate and induction of apoptosis. Furthermore, treatment of the medulloblastoma cell lines and medulloblastoma stem cells with amiodarone and gambogic acid, two inhibitors of this class of Kir channels, phenocopied these effects in a time- and dose-dependent manner. Whole cell patch clamp results revealed a nearly complete current blockade upon inhibitor treatment. Subsequently, we showed that pharmacological inhibition of KCNJ2 and knockdown KCNJ2 significantly reduced tumor growth and resulted in prolonged survival in an orthotopic medulloblastoma mouse model. In summary, our data suggest that pharmacological inhibition of KCNJ2 may constitute a new therapeutic option for patients with high-risk medulloblastomas. Citation Format: Francesca Valdora, Florian Freier, Livia Garzia, Vijay Ramaswamy, Claudia Seyler, Thomas Hielscher, Nathan Brady, Paul A. Northcott, Marcel Kool, David TW Jones, Hendrik Witt, Gian Paolo Tonini, Wolfram Scheurlen, Hugo A. Katus, Andreas E. Kulozik, Edgar Zitron, Andrey Korshunov, Peter Lichter, Michael D. Taylor, Stefan M. Pfister, Marc Remke. KCNJ2 constitutes a marker and therapeutic target of high-risk medulloblastomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5050. doi:10.1158/1538-7445.AM2013-5050
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-5050
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
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    Abstract 4591: Whole genome sequencing of SHH medulloblastomas predicts molecular groups of responders and non-responders to SMO-inhibition .
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4591-4591
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 4591-4591
    Abstract: Recently, we and others analyzed large series of pediatric medulloblastomas (MB) and identified a number of recurrent aberrations in each of the four major subgroups (WNT, SHH, Group 3 and Group 4). However, due to their infrequent occurrence not much is known about genetic aberrations in adult MBs. We now have analyzed a large series of adult SHH MBs (age ≥ 16) by whole genome sequencing and compared them with pediatric SHH MBs. We sequenced tumor and blood of 26 adult SHH MBs and compared them with 30 pediatric SHH MBs. A replication cohort of 28 adult and 29 pediatric SHH MBs was sequenced for 414 genes by targeted sequencing. We also performed expression profiling and DNA methylation analyses on most of these cases. Whole genome sequencing revealed a clear correlation between mutation rate and age of the patient (r = 0.69). Furthermore, the genomic data showed that SHH MBs can be split up in three distinct subgroups: infants, children and adults. They all have mutations in the SHH pathway, mostly in PTCH1 (infants and adults), SUFU (infants) and SMO (adults). Children almost completely lack the classical upstream SHH pathway mutations but instead have more downstream aberrations such as MYCN and GLI2 mplifications, and have frequent TP53 mutations, often in the germline, whilst all of these were extraordinarily rare in infants and adults. We also identified several recurrent mutations in adult MBs that were not found in pediatric MBs. Moreover, the three SHH subgroups were different in their transcriptome and methylome with the TP53 mutated SHH MBs in children being more similar to adult MBs. Collectively, this data will help to better understand the biology of pediatric and adult SHH-medulloblastoma, but most importantly may help selecting patients for targeted SHH inhibition and new treatment strategies for TP53 mutated SHH MBs in a clinical setting. Citation Format: Marcel Kool, David TW Jones, Natalie Jaeger, Paul A. Northcott, Volker Hovestadt, Ulrich Schueller, Marc Remke, Yoon-Jae Cho, Scott Pomeroy, Michael D. Taylor, Roland Eils, Andrey Korshunov, Peter Lichter, Stefan M. Pfister. Whole genome sequencing of SHH medulloblastomas predicts molecular groups of responders and non-responders to SMO-inhibition . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4591. doi:10.1158/1538-7445.AM2013-4591
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-4591
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 9
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    Abstract LB-B23: Medulloblastoma regulatory circuitries reveal subgroup-specific cellular origins
    American Association for Cancer Research (AACR) ; 2015
    In:  Molecular Cancer Therapeutics Vol. 14, No. 12_Supplement_2 ( 2015-12-01), p. LB-B23-LB-B23
    Details
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 14, No. 12_Supplement_2 ( 2015-12-01), p. LB-B23-LB-B23
    Abstract: Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating consequences on the developing child. Genomic studies have revealed four distinct molecular subgroups with divergent biology and clinical behaviour. An understanding of the regulatory circuitry governing the transcriptional landscapes of medulloblastoma subgroups, and how this relates to their respective developmental origins, is currently lacking. Using H3K27ac and BRD4 ChIP-Seq, coupled with tissue-matched DNA methylation and transcriptome data, we describe the active cis-regulatory landscape across 28 primary medulloblastoma specimens. Analysis of differentially regulated enhancers and super-enhancers reinforced inter-subgroup heterogeneity and revealed novel, clinically relevant insights into medulloblastoma biology. Computational reconstruction of core regulatory circuitry identified a master set of transcription factors responsible for subgroup divergence that validated by ChIP-Seq and implicated candidate cells-of-origin for Group 4. Our integrated analysis of cis-regulatory elements in a large series of primary tumour samples reveals insights into cis-regulatory architecture, unrecognized dependencies, and cellular origins. Citation Format: Charles Y. Lin, Serap Erkek, Yiai Tong, Linlin Yang, Alexander J. Federation, Marc Zapatka, Parthiv Haldipur, Daisuke Kawauchi, Thomas Risch, Hans-Jörg Warnatz, Barbara Worst, Bensheng Ju, Brent A. Orr, Rhamy Zeid, Donald R. Polaski, Maia Segura-Wang, Sebastian M. Waszak, David TW Jones, Marcel Kool, Volker Hovestadt, Ivo Buchhalter, Laura Sieber, Pascal Johann, Stefan Gröschel, Marina Ryzhova, Andrey Korshunov, Wenbiao Chen, Victor V. Chizhikov, Kathleen J. Millen, Vyacheslav Amstislavskiy, Hans Lehrach, Marie-Laure Yaspo, Roland Eils, Peter Lichter, Jan O. Korbel, Stefan Pfister, James E. Bradner, Paul A. Northcott. Medulloblastoma regulatory circuitries reveal subgroup-specific cellular origins. [abstract] . In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-B23.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    URL: Article
    DOI: 10.1158/1535-7163.TARG-15-LB-B23
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2062135-8
    SSG: 12
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  • 10
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    Abstract 3447: FSTL5 improves prognostic subclassification of medulloblastoma
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3447-3447
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3447-3447
    Abstract: Current integrated genomic approaches indicate distinct biological variants in medulloblastoma. Comprehensive molecular classification strategies utilize cytogenetic or immunohistochemical biomarkers to refine risk stratification. Novel complementary markers may ameliorate outcome prediction particularly in intermediate or high-risk medulloblastomas. We combined transcriptome and DNA copy-number analysis for 64 primary tumors. Bioinformatic tools were applied to investigate marker genes of molecular variants. Differentially expressed transcripts were evaluated for prognostic value in the entire screening cohort. Immunohistochemical markers were used to determine molecular subtypes in adult and pediatric medulloblastoma samples (n=235). Immunopositivity of FSTL5 was correlated with molecular and prognostic subgroups for 235 non-overlapping medulloblastoma samples on two independent tissue microarrays (TMA). Unsupervised cluster analyses of transcriptome profiles revealed four distinct molecular variants: WNT, SHH, Group C, and Group D. Stable subgroup separation was achieved using only 300 most varying transcripts. Specific distribution of clinical and molecular characteristics was noted for each cluster. Notably, Group C tumors were exclusively present in pediatric medulloblastomas as determined by immunohistochemistry. Delimited expression patterns of FSTL5 in each molecular subgroup were confirmed by quantitative real-time PCR. FSTL5 transcripts were most up-regulated in Group C and Group D tumors with unfavorable prognosis, whereas WNT medulloblastomas showed marked down-regulation. Immunopositivity of FSTL5 identified a large proportion of patients (84 of 235 patients; 36%) at high risk for relapse and death in particular in patients with WNT/SHH-independent tumors. Multivariate analysis revealed that FSTL5 immunopositivity constitutes an independent prognostic marker in pediatric and adult patient cohorts (p & lt;0.0001). Importantly, adding this biomarker to comprehensive outcome prediction schemes substantially reduced the prediction error of the model. Comprehensive analyses of transcriptome and genetic alterations unravel four distinct disease variants. By addition of FSTL5 immunohistochemistry, existing molecular stratification schemes can effectively be complemented and sub-classification of WNT/SHH-independent tumors substantially optimized. This approach may ultimately define clear risk groups to individualize treatment intensities in future clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3447. doi:10.1158/1538-7445.AM2011-3447
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-3447
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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