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EGFR Gene (egfr + gene)
Selected AbstractsCentral neurocytomas are genetically distinct from oligodendrogliomas and neuroblastomasHISTOPATHOLOGY, Issue 2 2000C Y K Tong Aims Central neurocytoma is a rare central nervous system tumour typically found in the lateral ventricles and at the septum pellucidum. Histologically, it resembles oligodendrogliomas and yet ultrastructurally, it shows neuronal differentiation. Its molecular oncogenesis is not known. The aim of this study was to examine whether major genetic events found in oligodendrogliomas and neuronal tumours, namely allelic deletions of chromosomes 1p and 19q and N-myc amplification, can be found in central neurocytomas. As there was one report describing gain of chromosome 7 in central neurocytomas, we also examined epidermal growth factor receptor (EGFR) amplification, as the EGFR gene is located at chromosome 7p. Methods and results Nine central neurocytomas and matched blood samples were examined for loss of heterozygosity (LOH) of 1p and 19q13.2,13.4 with 23 finely mapped microsatellite markers. N-myc amplification was studied by fluorescence in-situ hybridization using paraffin-embedded sections. EGFR amplification was tested for by differential PCR. Six of nine (67%) tumours showed LOH at one or more loci at 1p and 5/9 (56%) of cases showed LOH at 19q. However, common regions of deletion cannot be identified. The majority of informative markers are retained at 1p (84%) and 19q (86%). Only one tumour showed amplification of N-myc and none of the cases showed amplification of EGFR. Conclusion Central neurocytomas are genetically distinct from oligodendrogliomas, and chromosomes 1p and 19q probably do not play an important role in their pathogenesis. N-myc and EGFR amplification are rare. [source] Fluorescent in situ hybridization mapping of the epidermal growth factor receptor gene in donkeyJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 3 2007M. Bugno Summary The physical localization of the epidermal growth factor receptor (EGFR) gene was performed on donkey chromosomes. Bacterial artificial chromosome DNA containing the equine EGFR gene was used to map this gene by fluorescent in situ hybridization on donkey metaphase chromosomes. The gene was mapped on donkey 1q21.1 region. [source] Amplification of the epidermal growth factor receptor gene in glioblastoma: An analysis of the relationship between genotype and phenotype by CISH methodNEUROPATHOLOGY, Issue 2 2008Tomomi Miyanaga We examined epidermal growth factor receptor (EGFR) overexpression and EGFR gene amplification using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in 109 glioblastomas, including 98 primary glioblastomas and 11 secondary glioblastomas. EGFR overexpression and EGFR gene amplification were found in 33% and 24% of glioblastoma, respectively, and all of those cases were primary glioblastoma. Large ischemic necrosis was significantly more frequent in primary glioblastomas than in secondary glioblastomas (54% vs. 18%), but pseudopalisading necrosis was not (65% vs. 54%). EGFR gene amplification was detected significantly more frequently in cases with both types of necrosis. Although glioblastomas with EGFR gene amplification invariably exhibited EGFR overexpression at the level of the whole tumor, tumor cells with EGFR gene amplification did not always show EGFR overexpression at the level of individual tumor cells. Cases of "strong" EGFR overexpression on IHC could be regarded as having EGFR gene amplification, and cases without EGFR overexpression could not. Cases of "weak" EGFR overexpression should be tested with CISH to confirm the presence of EGFR gene amplification. We found that 54% of glioblastomas with EGFR gene amplification were composed of areas with and without EGFR gene amplification; however, there were no obvious differences in morphology between tumor cells with and without EGFR gene amplification. Although small cell architecture might be associated with EGFR gene amplification at the level of the whole tumor, it did not always suggest amplification of the EGFR gene at the level of individual tumor cells. In one case, it seemed to suggest that a clone with EGFR gene amplification may arise in pre-existing tumor tissue and extend into the surrounding area. In cases of overall EGFR amplification, CISH would be a useful tool to decide the tumor border in areas infiltrated by tumor cells. [source] Predominant Expression of Mutant EGFR (EGFRvIII) is Rare in Primary GlioblastomasBRAIN PATHOLOGY, Issue 2 2004Wojciech Biernat EGFR amplification is a frequent genetic alteration in primary (de novo) glioblastomas, and is often associated with structural alterations. Most common is variant III (EGFRvIII), which results from a non-random 801 bp in-frame deletion of exons 2 to 7 of the EGFR gene. We assessed amplification and overexpression of EGFRvIII and wild-type EGFR in 30 glioblastoma biopsies. Immunohistochemically, EGFR overexpression was observed in 20 (67%) of 30 glioblastomas. Eight (27%) cases also showed immunoreactivity to an EGFRvIII antibody. In 6 of these cases, the pattern of EGFR and EGFRvIII overexpression was compared in serial sections: In 4 cases, areas with immunoreactivity to EGFRvIII largely coincided with wild-type EGFR expression. In the other 2 cases, the areas immunoreactive to EGFRvIII were significantly less extensive than EGFR-positive areas. To assess whether EGFRvIII is predominantly amplified in tumors with concurrent wild-type EGFR amplification, we carried out real-time quantitative PCR using 2 sets of primers located in exon 2 and intron 15 of the EGFR gene. A>5-fold ratio of relative copy numbers between intron 15 (present both in wild-type EGFR and EGFRvIII) and exon 2 (present only in wild-type EGFR, but missing in EGFRvIII) suggested predominant amplification of EGFRvIII in only 3 (10%) of 30 glioblastomas. The observation that intratumoral wild-type EGFR overexpression is often more extensive and that predominant amplification of EGFRvIII is a rare event would limit the effectiveness of therapeutic approaches based on selective targeting of EGFRvIII. [source] Serum carcinoembryonic antigen level is associated with epidermal growth factor receptor mutations in recurrent lung adenocarcinomasCANCER, Issue 12 2007Fumihiro Shoji MD Abstract BACKGROUND. The presence of epidermal growth factor receptor (EGFR) gene mutations is a good indicator of the clinical efficacy of gefitinib in patients with nonsmall cell lung cancer. It was recently reported that the serum carcinoembryonic antigen (CEA) level could be a predictive factor for the efficacy of gefitinib treatment; therefore, it is suggested that the EGFR gene mutation is associated with the serum CEA level. The current study analyzed the association between EGFR gene mutations and clinical features, including the serum CEA level, in patients with recurrent lung adenocarcinomas. METHODS. A total of 48 lung adenocarcinoma patients with postoperative disease recurrence who underwent chemotherapy were investigated. EGFR gene mutations at exons 18, 19, and 21 were measured using surgical specimens taken from the primary tumor. RESULTS. Mutations of the EGFR gene were detected in 25 of the 48 patients and the abnormal serum CEA concentration at the time of disease recurrence was found to be significantly associated with the incidence of EGFR gene mutations (P = .045). The rate of EGFR gene mutations significantly increased as the serum CEA level increased (serum CEA level; <5 vs ,5 <20 vs ,20 = 35% vs 55% vs 87.5%, respectively, P = .040). A multivariate analysis revealed that a higher serum CEA level at the time of disease recurrence is independently associated with EGFR gene mutations (P = .036) with an odds ratio of 4.70 (95% confidence interval, 1.1,21.1). CONCLUSIONS. The serum CEA level appears to be closely associated with the presence of EGFR gene mutations in patients with pulmonary adenocarcinomas. Cancer 2007. © 2007 American Cancer Society. [source] Clinical significance of pretreatment serum amphiregulin and transforming growth factor-,, and an epidermal growth factor receptor somatic mutation in patients with advanced non-squamous, non-small cell lung cancerCANCER SCIENCE, Issue 11 2008Katsuhiro Masago Circulating amphiregulin and transforming growth factor-, (TGF-,) have been found to be correlated with an unfavorable response to gefitinib based on the identification of patients with a higher probability of resistance to the drug. However, the association between an epidermal growth factor receptor (EGFR) somatic mutation and the overexpression of its ligands has not been determined. To verify the clinical significance of the two serum markers and EGFR mutation status, we determined serum amphiregulin and TGF-, levels by enzyme-linked immunosorbent assay in 93 patients with advanced non-squamous, non-small cell lung cancer and EGFR somatic mutation status using the peptic nucleic acid-locked nucleic acid clamp method in 46 cases. The relationship between each independent clinicopathological variable and the response to gefitinib therapy was examined. We also evaluated the risk factors associated with prognosis. Fourteen (41.0%) of 34 progressive disease cases were positive for amphiregulin (P = 0.007). Eleven (32.4%) of 34 progressive disease cases were positive for TGF-, (P = 0.005). The median survival time of patients with the EGFR somatic mutation was significantly longer (P = 0.01). The same was true of amphiregulin- (P = 0.046) and TGF-,-negative patients (P < 0.01). In multivariate analysis, serum TGF-, positivity (hazard ratio, 2.558; P = 0.005) and the wild type EGFR gene (hazard ratio, 1.894; P = 0.003) were significant independent prognostic factors. Our study demonstrates that the status of the serum EGFR ligand, in addition to EGFR activating mutation, is a predictive factor for response to gefitinib therapy. (Cancer Sci 2008; 99: 2295,2301) [source] Epidermal growth factor receptor expression regulates proliferation in the postnatal rat retinaGLIA, Issue 2 2006Jennie L. Close Abstract Epidermal growth factor (EGF) is known to promote proliferation of both retinal progenitors and Muller glia in vitro, but several questions remain concerning an in vivo role for this factor. In this study, we investigated whether the EGF receptor (EGFR) is necessary for the maintenance of normal levels of progenitor and Muller glial proliferation in vivo. Here, we show that (1) mice with homozygous deletion of the Egfr gene have reduced proliferation in late stages of retinal histogenesis, (2) EGF is mitogenic for Müller glia in vivo during the first two postnatal weeks in the rodent retina, (3) the effectiveness of EGF as a Müller glial mitogen declines in parallel with the decline in EGFR expression as the retina matures, and (4) following damage to the retina from continuous light exposure, EGFR expression is up-regulated in Müller glia to levels close to those in the neonatal retina, resulting in a renewed mitotic response to EGF. Together with previous results from other studies, these data indicate that the downregulation of a growth factor receptor is one mechanism by which glial cells maintain mitotic quiescence in the mature nervous system. © 2006 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||