Abstract:
:Glioblastoma (GBM) is an incurable brain tumor for which new treatment strategies are urgently needed. Next-generation sequencing of GBM has most often been performed retrospectively and on archival tissue from both diagnostic and relapse surgeries with limited knowledge of clinical information, including treatment given. We sought to investigate the genomic composition prospectively in treatment-naïve patients, searched for possible targetable aberrations, and investigated for prognostic and/or predictive factors. A total of 108 newly diagnosed GBM patients were included. Clinical information, progression-free survival, and overall survival (OS) were noted. Tissues were analyzed by whole-exome sequencing, single nucleotide polymorphism (SNP) and transcriptome arrays, and RNA sequencing; assessed for mutations, fusions, tumor mutational burden (TMB), and chromosomal instability (CI); and classified into GBM subgroups. Each genomic report was discussed at a multidisciplinary tumor board meeting to evaluate for matching trials. From 111 consecutive patients, 97.3% accepted inclusion in this study. Eighty-six (77%) were treated with radiation therapy/temozolomide (TMZ) and adjuvant TMZ. One NTRK2 and three FGFR3-TACC3 fusions were identified. Copy number alterations in GRB2 and SMYD4 were significantly correlated with worse median OS together with known clinical variables like age, performance status, steroid dose, and O6-methyl-guanine-DNA-methyl-transferase status. Patients with CI-median or TMB-high had significantly worse median OS compared to CI-low/high or TMB-low/median. In conclusion, performing genomic profiling at diagnosis enables evaluation of genomic-driven therapy at the first progression. Furthermore, TMB-high or CI-median patients had worse median OS, which can support the possibility of offering experimental treatment already at the first line for this group.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Nørøxe DS,Yde CW,Østrup O,Michaelsen SR,Schmidt AY,Kinalis S,Torp MH,Skjøth-Rasmussen J,Brennum J,Hamerlik P,Poulsen HS,Nielsen FC,Lassen Udoi
10.1002/1878-0261.12790subject
Has Abstractpub_date
2020-09-04 00:00:00eissn
1574-7891issn
1878-0261pub_type
杂志文章abstract::Cullin 4B, a member of the Cullins, which serve as scaffolds to facilitate the assembly of E3 ligase complexes, is aberrantly expressed in many cancers, including osteosarcoma. Recently, we observed that CUL4B forms the CRL4BDCAF11 E3 ligase, which specifically ubiquitinates and degrades the cyclin-dependent kinase (C...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12176
更新日期:2018-04-01 00:00:00
abstract::Endocytosis is an important regulator of cell-cell signaling and endocytic trafficking has been increasingly implicated in control of tumor suppression. Recent insights from Drosophila indicate that impairment of multiple trafficking steps which lead to receptor degradation can cause tumor formation in epithelial orga...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2009.05.005
更新日期:2009-08-01 00:00:00
abstract::C4.4A is a metastasis-associated molecule that functions appear to rely on associated alph6beta4 integrin. To corroborate the impact of the C4.4A-alpha6beta4 integrin association on metastasis formation, C4.4A was knocked-down in a highly metastatic rat pancreatic adenocarcinoma (ASML, ASML-C4.4Akd). Metastasis format...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2013.05.002
更新日期:2013-10-01 00:00:00
abstract::We describe a cell damage-induced phenotype in mammary carcinoma cells involving acquisition of enhanced migratory and metastatic properties. Induction of this state by radiation required increased activity of the Ptgs2 gene product cyclooxygenase 2 (Cox2), secretion of its bioactive lipid product prostaglandin E2 (PG...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12321
更新日期:2018-08-01 00:00:00
abstract::Estrogen receptor-alpha (ERα)-positive breast cancer is often treated with antihormonal regimens. However, resistance to treatment is common, leading to metastatic disease. ERα activity requires the functional involvement of pioneer factors FOXA1 and GATA3, which enable ERα-chromatin binding and are crucial for ERα-dr...
journal_title:Molecular oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1002/1878-0261.12353
更新日期:2018-11-01 00:00:00
abstract:PURPOSE:Lobular carcinoma in situ (LCIS) is both a risk indicator and non-obligate precursor of invasive lobular carcinoma (ILC). We sought to characterize the transcriptomic features of LCIS and ILC, with a focus on the identification of intrinsic molecular subtypes of LCIS and the changes involved in the progression ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.12.005
更新日期:2015-04-01 00:00:00
abstract::The absence of biomarkers to accurately predict anticancer therapy response remains a major obstacle in clinical oncology. We applied a genome-wide loss-of-function screening approach in human haploid cells to characterize genetic vulnerabilities to classical microtubule-targeting agents. Using docetaxel and vinorelbi...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12307
更新日期:2018-06-01 00:00:00
abstract::Due to the speed, efficiency, relative risk, and lower costs compared to traditional drug discovery, the prioritization of candidate drugs for repurposing against cancers of interest has attracted the attention of experts in recent years. Herein, we present a powerful computational approach, termed prioritization of c...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12564
更新日期:2019-10-01 00:00:00
abstract::Endoplasmic reticulum (ER) stress is an adaptive response to various stress conditions and plays emerging roles in cancer. Activating transcription factor 6 (ATF6), one of the three major ER stress transducers, has been shown to contribute to chemoresistance by altering cancer cell survival. Cancerous inhibitor of pro...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12365
更新日期:2018-10-01 00:00:00
abstract::Mammalian cells can release different types of extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies. Accumulating evidence suggests that EVs play a role in cell-to-cell communication within the tumor microenvironment. EVs' components, such as proteins, noncoding RNAs [microRNAs (miRNAs...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1002/1878-0261.12144
更新日期:2017-12-01 00:00:00
abstract::The MYC protein is a transcription factor with oncogenic potential controlling fundamental cellular processes such as cell proliferation, metabolism, differentiation, and apoptosis. The MYC gene is a major cancer driver, and elevated MYC protein levels are a hallmark of most human cancers. We have previously shown tha...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12636
更新日期:2020-03-01 00:00:00
abstract::As a critical feature of the tumor microenvironment, hypoxia is known to be a potent inducer of tumor metastasis, and it has been proposed that the initial steps in metastasis involve epithelial-mesenchymal transition (EMT). The strong correlation among hypoxia, EMT, and metastasis suggests that integrative assessment...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12491
更新日期:2019-07-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is an important process in embryonic development, fibrosis, and cancer metastasis. During cancer progression, the activation of EMT permits cancer cells to acquire migratory, invasive, and stem-like properties. A growing body of evidence supports the critical link between EMT an...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1002/1878-0261.12096
更新日期:2017-07-01 00:00:00
abstract::Prostate cancer (PCa) remains an important public health concern in Western countries. Metabolic syndrome (MeS) is a cluster of pathophysiological disorders with increasing prevalence in the general population that is a risk factor for PCa. Several studies have determined that a crosstalk between white adipose tissue ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12788
更新日期:2020-09-02 00:00:00
abstract:INTRODUCTION:Most analyses of high throughput cancer data represent tumors by "atomistic" single-gene properties. Pathifier, a recently introduced method, characterizes a tumor in terms of "coarse grained" pathway-based variables. METHODS:We applied Pathifier to study a very large dataset of 2000 breast cancer samples...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.04.006
更新日期:2015-08-01 00:00:00
abstract::The let-7 microRNA (miRNA) family has been implicated in the regulation of diverse cellular processes and disease pathogenesis. In cancer, loss-of-function of let-7 miRNAs has been linked to tumorigenesis via increased expression of target oncogenes. Excessive proliferation rate of tumor cells is often associated with...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.01.005
更新日期:2015-06-01 00:00:00
abstract::DNA ploidy analysis is useful for prognostication in cancer patients, but the genomic details underlying ploidy changes are not fully understood. To improve this understanding, we compared DNA ploidy status with karyotypic and comparative genomic hybridization data on 51 endometrial adenocarcinomas. Out of 34 DNA dipl...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2011.10.002
更新日期:2012-02-01 00:00:00
abstract::Breast cancer (BrCa) metabolism is geared toward biomass synthesis and maintenance of reductive capacity. Changes in glucose and glutamine metabolism in BrCa have been widely reported, yet the contribution of fatty acids (FAs) in BrCa biology remains to be determined. We recently reported that adipocyte coculture alte...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12368
更新日期:2018-09-01 00:00:00
abstract::cMet is a well-characterized oncogene that is the target of many drugs including small molecule and biologic pathway inhibitors, and, more recently, antibody-drug conjugates (ADCs). However, the clinical benefit from cMet-targeted therapy has been limited. We developed a novel cMet-targeted 'third-generation' ADC, TR1...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12600
更新日期:2020-01-01 00:00:00
abstract::The abnormal expression of long noncoding RNAs (lncRNAs) is associated with human carcinoma. The present study aimed to investigate the mechanisms underlying the function of lncRNA AK002107 in the progression of hepatocellular carcinoma (HCC). The differential expression of lncRNAs between HCC and paired nontumor tiss...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12487
更新日期:2019-05-01 00:00:00
abstract::The PI3K/Akt signaling pathway, the most frequently altered signaling system in human cancer, is a crucial inducer of dysregulated proliferation and neoplastic processes; however, few therapeutic strategies using PI3K/Akt inhibitors singly have been shown to be effective. The purpose of this paper was to underline the...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12888
更新日期:2020-12-18 00:00:00
abstract::Epigenetic silencing of miRNA is a primary mechanism of aberrant miRNA expression in cancer, and hypermethylation of miRNA promoters has been reported to contribute to prostate cancer initiation and progression. Recent data have shown that the miR-193b promoter is hypermethylated in prostate cancer compared with norma...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12536
更新日期:2019-09-01 00:00:00
abstract::Epigenetic changes can be defined as stable molecular alterations of a cellular phenotype such as the gene expression profile of a cell that are heritable during somatic cell divisions (and sometimes germ line transmissions) but do not involve changes of the DNA sequence itself. Epigenetic phenomena are mediated by se...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2010.04.002
更新日期:2010-06-01 00:00:00
abstract::miRNAs in circulating extracellular vesicles (EVs) are promising biomarkers for cancer. However, their diagnostic ability for early-stage non-small-cell lung cancer (NSCLC) is not well known. In this study, the circulating EV miRNAs profiling was initially performed in 36 untreated NSCLC patients and 36 healthy contro...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12889
更新日期:2020-12-19 00:00:00
abstract::Short arm of chromosome 8 is a hot spot for chromosomal breaks, losses and amplifications in breast cancer. Although such genetic changes may have phenotypic consequences, the identity of candidate gene(s) remains to be clearly defined. Pol β gene is localized to chromosome 8p12-p11 and encodes a key DNA base excision...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.01.001
更新日期:2014-05-01 00:00:00
abstract::Comprehensive Cancer Centres (CCCs) serve as critical drivers for improving cancer survival. In Europe, we have developed an Excellence Designation System (EDS) consisting of criteria to assess "excellence" of CCCs in translational research (bench to bedside and back), with the expectation that many European CCCs will...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2015.12.007
更新日期:2016-05-01 00:00:00
abstract::Thyroid transcription factor-1 (TTF-1, encoded by the NKX2-1 gene) is highly expressed in small-cell lung carcinoma (SCLC) and lung adenocarcinoma (LADC), but how its functional roles differ between SCLC and LADC remains to be elucidated. Here, we compared the genome-wide distributions of TTF-1 binding regions and the...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12608
更新日期:2020-02-01 00:00:00
abstract::There is increasing evidence that glioblastoma possess 'stem-like' cells, low concentrations of which can initiate a tumour. It has been proposed that these cells are radioresistant, and that this property contributes to the poor treatment outcomes of these tumours. In this paper we propose that radioresistance is not...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2011.05.001
更新日期:2011-08-01 00:00:00
abstract::Infiltration of the tumor microenvironment by nerve fibers is an understudied aspect of breast carcinogenesis. In this study, the presence of nerve fibers was investigated in a cohort of 369 primary breast cancers (ductal carcinomas in situ, invasive ductal and lobular carcinomas) by immunohistochemistry for the neuro...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.05.001
更新日期:2015-10-01 00:00:00
abstract::Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLeX/A ), and α-1,3/4-fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12163
更新日期:2018-05-01 00:00:00