Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-6-16
pubmed:abstractText
Several molecular and histopathological prognostic markers have been proposed for the therapeutic stratification of medulloblastoma patients. Amplification of the c-myc oncogene, elevated levels of c-myc mRNA, or tumor anaplasia have been associated with worse clinical outcomes. In contrast, high TrkC mRNA expression generally presages longer survival. The goal of this study was to evaluate the prognostic value of c-myc, N-myc and TrkC expression in medulloblastomas and compare them to histopathological classification. We used in situ hybridization to measure expression of these molecular markers. c-myc mRNA was detected in 18 of 59 (31%) cases, and was significantly associated with shorter patient survival times on both univariate and multivariate analyses (p = 0.04). The presence of c-myc mRNA was also significantly associated with tumor anaplasia. While survival rates were higher for patients with low N-myc or high TrkC expression, these differences were not statistically significant. The group of patients with either moderate or severely anaplastic tumors showed only a trend towards shorter survival (p = 0.11). However, severe anaplasia alone was significantly prognostic (p = 0.002). Given the prognostic import of c-myc, we investigated 2 potential mechanisms by which its expression might be regulated: Wnt signaling and Mxi-1 mutation. Nuclear translocation of beta-catenin, a marker of Wnt pathway activation, was more common in medulloblastomas with high c-myc than in tumors overall, but the difference was not statistically significant. No Mxi-1 mutations were detected in the 22 cases examined. The association we describe between c-myc expression, tumor anaplasia, and worse clinical outcomes provides further evidence for the importance of this oncogene in medulloblastoma pathobiology.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix..., http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/MXI1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/MYC protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, trkC, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Markers, Biological, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Zebrafish Proteins, http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3069
pubmed:author
pubmed:issnType
Print
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
441-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15198123-Active Transport, Cell Nucleus, pubmed-meshheading:15198123-Adolescent, pubmed-meshheading:15198123-Adult, pubmed-meshheading:15198123-Anaplasia, pubmed-meshheading:15198123-Basic Helix-Loop-Helix Transcription Factors, pubmed-meshheading:15198123-Cerebellar Neoplasms, pubmed-meshheading:15198123-Child, pubmed-meshheading:15198123-Child, Preschool, pubmed-meshheading:15198123-Cytoskeletal Proteins, pubmed-meshheading:15198123-DNA-Binding Proteins, pubmed-meshheading:15198123-Female, pubmed-meshheading:15198123-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15198123-Humans, pubmed-meshheading:15198123-Infant, pubmed-meshheading:15198123-Male, pubmed-meshheading:15198123-Medulloblastoma, pubmed-meshheading:15198123-Predictive Value of Tests, pubmed-meshheading:15198123-Prognosis, pubmed-meshheading:15198123-Proto-Oncogene Proteins, pubmed-meshheading:15198123-Proto-Oncogene Proteins c-myc, pubmed-meshheading:15198123-RNA, Messenger, pubmed-meshheading:15198123-Receptor, trkC, pubmed-meshheading:15198123-Survival Rate, pubmed-meshheading:15198123-Trans-Activators, pubmed-meshheading:15198123-Transcription Factors, pubmed-meshheading:15198123-Tumor Markers, Biological, pubmed-meshheading:15198123-Tumor Suppressor Proteins, pubmed-meshheading:15198123-Up-Regulation, pubmed-meshheading:15198123-Wnt Proteins, pubmed-meshheading:15198123-Zebrafish Proteins, pubmed-meshheading:15198123-beta Catenin
pubmed:year
2004
pubmed:articleTitle
Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia.
pubmed:affiliation
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. ceberha@jhmi.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't