Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diffuse astrocytoma WHO grade II is a well-differentiated, slowly growing tumor that has an inherent tendency to progress to anaplastic astrocytoma (WHO grade III) and, eventually, to glioblastoma (WHO grade IV). Little is known about its molecular basis, except for p53 mutations that are found in >60% of cases. In a search for additional genetic alterations, we carried out gene expression profiling of 11 diffuse astrocytomas using cDNA expression arrays. Expression of six genes (TIMP3, c-myc, EGFR, DR-nm23, nm23-H4, and GDNPF) was detected in 64-100% of diffuse astrocytomas, but not in nontumorous brain tissue. Seven genes (AAD14, SPARC, LRP, PDGFR-alpha, 60S ribosomal protein L5, PTN, and hBAP) were found to be up-regulated more than 2-fold in 20-60% of cases, whereas 11 genes (IFI 9-27, protein kinase CLK, TDGF1, BIN1, GAB1, TYRO3, LDH-A, adducin 3, GUK1, CDC10, and KRT8) were down-regulated to less than 50% of normal levels in 64-100% of cases. Semiquantitative conventional reverse transcription-PCR was performed for 11 genes, 9 of which showed an expression profile similar to that obtained with cDNA expression arrays. Immunohistochemical staining for SPARC showed cytoplasmic immunoreactivity of neoplastic cells in all diffuse astrocytomas analyzed. These results indicate significant changes in gene expression in diffuse astrocytomas, but it remains to be shown which of these are causally related to the transformation of glial cells.
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PMID:Gene expression profiling of low-grade diffuse astrocytomas by cDNA arrays. 1115 82

The histological diagnosis of low-grade astrocytomas and oligodendrogliomas (WHO grade II) is often challenging, particularly in cases that show both astrocytic and oligodendroglial differentiation. We carried out gene expression profiling on 17 oligodendrogliomas (93% with LOH 1p and/or 19q) and 15 low-grade astrocytomas (71% with a TP53 mutation), using a cDNA array containing 1176 cancer-related genes. In oligodendrogliomas, 40 genes showed on average higher expression (at least a two-fold increase) than in astrocytomas, including DES, TDGF1, TGF-beta, GABA-BR1A, Histone H4, CDKN1A, PCDH43, Rho7 and Jun-D, while 39 genes were expressed at lower levels (at least a two-fold decrease), including JNK2, ITGB4, JNK3A2, RhoC, IFI-56K, AAD14 and EGFR. Immunohistochemistry revealed nuclear staining of Jun-D in oligodendrogliomas, in contrast to the immunoreactivity of cytoplasm and cell processes in low-grade astrocytomas. Partial least-squares analysis of the 79 genes at least two-fold differentially expressed between oligodendrogliomas and low-grade astrocytomas demonstrated perfect separation of oligodendrogliomas from low-grade astrocytomas and normal cerebral white matter. Clustering analysis based on the entire gene set divided the 17 subjects with oligodendrogliomas into two subgroups with significantly different survival (log-rank test, P=0.0305; survival to 5-years, 80 vs 0%, P=0.048). These results demonstrate that oligodendrogliomas and low-grade astrocytomas differ in their gene expression profiles, and that there are subgroups of oligodendroglioma with distinct expression profiles related to clinical outcome.
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PMID:Gene expression profiling and subgroup identification of oligodendrogliomas. 1520 79