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Updated: Jul 17, 2026
Evaluation of Lung Metastasis in Mouse Mammary Tumor Models by Quantitative Real-time PCR
Published on: January 29, 2016
EGFR sequence variations and real-time quantitative polymerase chain reaction analysis of gene dosage in brain
Carmen Franco-Hernandez1, Victor Martinez-Glez, Dolores Arjona
1Molecular Oncogenetics Laboratory, Research Unit, University Hospital La Paz, Paseo Castellana 261, 28046 Madrid, Spain.
Abstract:
Clinical response to Gefitinib (Iressa, ZD1839) has been found to be associated with somatic mutations, primarily of exons 18-21, of the epidermal growth factor receptor gene (EGFR) in non-small cell lung cancer (NSCLC). Evidence of a positive response was also reported recently on a patient with brain metastasis from NSCLC. On the other hand, amplification of EGFR appears to be associated with a poor prognosis. To determine whether EGFR mutations and amplification are involved in the tumorigenesis of brain metastases, we performed polymerase chain reaction/single-strand conformation polymorphism to examine exons 1, 2, and 7-26 of EGFR in a series of 18 brain metastases. The metastases derived from malignant melanoma (three cases), lung carcinoma (six cases), breast carcinoma (three cases), ovarian carcinoma (two cases), and one each from colon, kidney, bladder, and undifferentiated carcinoma. In addition to several sequence polymorphisms, we identified two mutations on E19 consisting of 18-base pair (bp) deletions: 2423-24440del and 2426-2443del. These mutations presented in lesions derived from kidney carcinoma and lung adenocarcinoma. By real-time quantitaive polymerase chain reaction technique, we determined the amplification/overdose status of EGFR by analyzing exons 11 and 25. Amplification (5- to 100-fold) was identified in three tumors, and overdose (low-level gene amplification corresponding to increases of 1- to 5-fold) presented in four additional metastases. These findings suggest that EGFR mutations and polymorphisms are not exclusively present in metastases derived from lung carcinoma. Accordingly, targeting of EGFR to determine molecular alterations of this gene may be useful in the management of patients with brain metastases.
Insights
Epidermal growth factor receptor (EGFR) mutations and amplification are found in brain metastases beyond lung cancer. These molecular alterations in EGFR may guide treatment for brain metastasis patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clinical response to Gefitinib in non-small cell lung cancer (NSCLC) is linked to epidermal growth factor receptor (EGFR) gene mutations.
- EGFR amplification is associated with a poor prognosis, while mutations can indicate a positive response.
- Previous studies have focused on EGFR in NSCLC, with limited data on its role in brain metastases from various primary cancers.
Purpose of the Study:
- To investigate the involvement of EGFR mutations and amplification in the tumorigenesis of brain metastases.
- To determine if EGFR alterations are specific to lung carcinoma metastases or present in metastases from other cancer types.
- To assess the potential of targeting EGFR for managing brain metastases.
Main Methods:
- Analysis of EGFR exons 1, 2, and 7-26 using polymerase chain reaction/single-strand conformation polymorphism in 18 brain metastases.
- Tumor samples included metastases from lung carcinoma, malignant melanoma, breast carcinoma, ovarian carcinoma, colon, kidney, bladder, and undifferentiated carcinoma.
- Real-time quantitative polymerase chain reaction was used to determine EGFR amplification/overdose status of exons 11 and 25.
Main Results:
- Two EGFR mutations (18-base pair deletions in exon 19) were identified in brain metastases from kidney carcinoma and lung adenocarcinoma.
- EGFR amplification (5- to 100-fold) was detected in three tumors.
- Low-level gene amplification (1- to 5-fold increase), termed overdose, was observed in four additional metastases.
- Sequence polymorphisms in EGFR were also identified across various tumor types.
Conclusions:
- EGFR mutations and polymorphisms are not exclusive to lung carcinoma brain metastases.
- The presence of EGFR alterations in brain metastases from diverse primary cancers suggests a broader role.
- Targeting EGFR and assessing its molecular alterations could be a valuable strategy in managing patients with brain metastases.
