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Results for “EGFR mutation”

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At least 55 records · Page 3Linked to original sources
PubMed2025

Unusual relapse dynamics in EGFR-mutated lung adenocarcinoma uncovered by genomic profiling: Insights from a case report.

Synchronous or metachronous multiple NSCLCs challenge clinical practice, particularly in distinguishing multiple separate primary lung cancers (SPLC) from intrapulmonary metastasis (IPM) for accurate staging and management. Here, we present a unique case of three resected lung adenocarcinomas (LUAD) from a single patient collected at different time points, all harboring the same EGFR p.L858R somatic driver mutation but exhibiting distinct clonal trajectories. Whole exome sequencing (WES) analysis revealed that the first tumor was an independent primary tumor, while the latter two tumors were clonally related. Our findings highlight the complexity of tumor progression and provide insights into clonal heterogeneity. This report underscores the importance of genomic profiling for discriminating SPLC from IPM and emphasizes that the detection of a single shared driver mutation is not sufficient to prove metastasis.

Humans↗
PubMed2001

PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme.

BACKGROUND: Survival of patients with anaplastic astrocytoma is highly variable. Prognostic markers would thus be useful to identify clinical subsets of such patients. Because specific genetic alterations have been associated with glioblastoma, we investigated whether similar genetic alterations could be detected in patients with anaplastic astrocytoma and used to identify those with particularly aggressive disease. METHODS: Tissue specimens were collected from 174 patients enrolled in Mayo Clinic Cancer Center and North Central Cancer Treatment Group clinical trials for newly diagnosed gliomas, including 63 with anaplastic astrocytoma and 111 with glioblastoma multiforme. Alterations of the EGFR, PTEN, and p53 genes and of chromosomes 7 and 10 were examined by fluorescence in situ hybridization, semiquantitative polymerase chain reaction, and DNA sequencing. All statistical tests were two-sided. RESULTS: Mutation of PTEN, amplification of EGFR, and loss of the q arm of chromosome 10 were statistically significantly less common in anaplastic astrocytoma than in glioblastoma multiforme (P =.033, P =.001, and P<.001, respectively), and mutation of p53 was statistically significantly more common (P<.001). Univariate survival analyses of patients with anaplastic astrocytoma identified PTEN (P =.002) and p53 (P =.012) mutations as statistically significantly associated with reduced and prolonged survival, respectively. Multivariate Cox analysis of patients with anaplastic astrocytoma showed that PTEN mutation remained a powerful prognostic factor after adjusting for patient age, on-study performance score, and extent of tumor resection (hazard ratio = 4.34; 95% confidence interval = 1.82 to 10.34). Multivariate classification and regression-tree analysis of all 174 patients identified EGFR amplification as an independent predictor of prolonged survival in patients with glioblastoma multiforme who were older than 60 years of age. CONCLUSION: PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older patients with glioblastoma multiforme, respectively.

Adolescent↗
PubMed2006

Gefitinib response of erlotinib-refractory lung cancer involving meninges--role of EGFR mutation.

BACKGROUND: A 70-year-old Japanese-American woman who had never smoked was diagnosed with stage IV non-small-cell lung cancer with rib metastases. She had previously been well and she had no family history of malignancy. While receiving treatment with erlotinib, an epidermal growth factor receptor small-molecule inhibitor, she progressed and developed new brain metastases. She failed further chemotherapy treatments and subsequently developed extensive symptomatic leptomeningeal carcinomatosis associated with diplopia, hemiparesis, weight loss, and incontinence. INVESTIGATIONS: Chest X-ray, head and chest CT scan, R2 lymph-node biopsy, histopathology, immunohistochemistry, MRI of head and spine, lumbar puncture, laser microdissection and EGFR genomic DNA sequencing of the R2 lymph node and cerebrospinal fluid tumor cells. DIAGNOSIS: Erlotinib-refractory stage IV lung adenocarcinoma and end-stage symptomatic leptomeningeal metastases with a novel double L858R + E884K somatic mutation of the EGFR. MANAGEMENT: Carboplatin, paclitaxel and erlotinib, whole-brain radiotherapy, temozolomide with and without irinotecan, and gefitinib.

Adenocarcinoma↗
PubMed2000

p53 mutation, EGFR gene amplification and loss of heterozygosity on chromosome 10, 17 p in human gliomas.

OBJECTIVE: To further illustrate the roles of p53 gene, epidermal growth factor receptor (EGFR) gene and loss of heterozygosity (LOH) on chromosome 10 and 17 p in human glioma progression. METHODS: p53 mutations were scanned in 50 gliomas with various malignant grades using the polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) assay, and were confirmed by direct sequencing. LOH for chromosome 10, 17 p and amplification of the EGFR gene were also assessed using Southern blot analysis. RESULTS: p53 mutations were found in 9 of 17 high-grade astrocytomas (53%), 1 of 15 low-grade astrocytomas (7%), and the only subject of eppendymoblastoma but in none of the 10 medulloblastomas and 7 eppendymomas. The majority of gliomas (38/50) analyzed here retained both 17 p alleles. The frequency of p53 mutations was 13% in this group of tumors and increased to 50% (6/12) in tumors with one 17 p allele (P < 0.025). LOH on chromosome 10 was found in 35% (6/17) of high-grade astrocytomas, in 10% (1/10) of medulloblastomas, but in 0% of low-grade gliomas. EGFR gene amplification was found in 9 high-grade gliomas, 60% (6/9) of which also presented LOH for chromosome 10. CONCLUSIONS: These results indicate that p53 inactivation is a common genetic event in astrocytoma progression that may be more strongly associated with the progression of astrocytomas than with their origin. Absence of p53 mutations in 50% of the tumors with one 17 p allele suggests that a tumor suppressor gene other than p53 may be located on chromosome 17 p and involved in progression to malignancy of some gliomas. The loss of alleles on chromosome 10 and the amplification of the EGFR gene appear to be restricted to high-grade tumors, suggesting that these events may be related to tumor progression rather than initiation.

Brain Neoplasms↗
PubMed2006

Epidermal growth factor receptor (EGFR) antibody down-regulates mutant receptors and inhibits tumors expressing EGFR mutations.

Activating mutations in the kinase domain of the EGF receptor have been reported in non-small cell lung cancer. The majority of tumors expressing these mutants are sensitive to ATP mimetics that inhibit the EGFR tyrosine kinase. The effect of antibodies that bind to the ectodomain of the receptor is less clear. We report herein the effects and mechanisms of action of the antibody cetuximab in lung cancer cells that naturally express receptor mutations and in ErbB-null 32D hematopoietic cells transfected with mutant EGFR. Treatment with cetuximab down-regulated EGFR levels and inhibited cell growth both in vitro and in vivo. This was associated with inhibition of ligand-independent EGFR signaling. These effects were seen in 32D cells arguing the growth inhibitory action was not because of the blockade of autocrine ligand action. Both antibody-induced EGFR down-regulation and inhibition of growth required receptor dimerization as monovalent Fab fragments only eliminated receptor levels or reduced cell proliferation in the presence of antihuman IgG. Finally, cetuximab inhibited growth of H1975 lung cancer cells and xenografts, which expressed L858R/T790M EGFR and were resistant to EGFR tyrosine kinase inhibitors. These data suggest that cetuximab is an effective therapy against mutant EGFR-expressing cancer cells and thus can be considered in combination with other anti-EGFR molecules.

Animals↗
PubMed2004

Velvet, a dominant Egfr mutation that causes wavy hair and defective eyelid development in mice.

In the course of a large-scale program of ENU mutagenesis, we isolated a dominant mutation, called Velvet. The mutation was found to be uniformly lethal to homozygotes, which do not survive E13.5. Mice heterozygous for the Velvet mutation are born with eyelids open and demonstrate a wavy coat and curly vibrissae. The mutation was mapped to the proximal end of chromosome 11 by genome-wide linkage analysis. On 249 meioses, the locus was confined to a 2.7-Mb region, which included the epidermal growth factor receptor gene (Egfr). An A --> G transition in the Egfr coding region of Velvet mice was identified, causing the amino acid substitution D833G. This substitution alters an essential triad of amino acids (DFG --> GFG) that is normally required for coordination of the ATP substrate. As such, kinase activity is at least mostly abolished, but quaternary structure of the receptor is presumably maintained, accounting for the dominant effect. Velvet is the first known dominant representative of the Egfr allelic series that is fully viable, a fact that makes it particularly useful for developmental studies.

Animals↗