Somatic Epidermal Growth Factor Receptor Research Articles

Low incidence of mutations in EGFR kinase domain in Caucasian patients with head and neck squamous cell carcinoma

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor ( EGFR) gene are associated with increased sensitivity to tyrosine kinase inhibitors (TKIs) and are present in 10–30% of non-small cell lung carcinoma depending on ethnic origin. EGFR protein is also overexpressed in about 90% of squamous cell carcinoma of head and neck (HNSCC), and treatment with TKIs has shown clinical benefit in a subgroup of these patients. Recently, EGFR mutations were described in three Asian patients with larynx cancer. We screened for EGFR tyrosine kinase mutations in tumour DNA of 100 patients of Caucasian origin with HNSCC by direct sequencing of the hotspot regions. Only one patient with larynx cancer displayed a novel, somatic EGFR missense mutation, K745R, affecting a highly conserved residue within the ATP cleft. Similar to reports in lung cancer, EGFR kinase domain mutations in HNSCC patients seem to show a lower incidence in patients of Caucasian origin.

O-184 Asian ethnicity, somatic epidermal growth factor receptor (EGFR) mutations and response to gefitinib in non-small cell lung cancer patients treated in a North American setting

O-184 Asian ethnicity, somatic epidermal growth factor receptor (EGFR) mutations and response to gefitinib in non-small cell lung cancer patients treated in a North American setting

Mutations of the epidermal growth factor receptor gene in atypical adenomatous hyperplasia and bronchioloalveolar carcinoma of the lung

A hypothesis of multistep carcinogenesis of lung adenocarcinoma from atypical adenomatous hyperplasia (AAH) to invasive adenocarcinoma through bronchioloalveolar carcinoma (BAC) has been proposed. However, the genetic alterations that play a role during these processes are not yet clear. Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in lung adenocarcinoma. We examined the status of EGFR mutations in AAH and BAC to elucidate the role they play during multistage of lung adenocarcinoma. We found somatic EGFR mutations in 3% (1/35) of AAH, 10.8% (4/37) of BAC and 41.9% (13/31) of invasive adenocarcinoma. Sixteen of 18 EGFR mutations were found in exon 19 and two were in exon 21. Among the 16 EGFR mutations in exon 19, 13 were deletions of 15bp and one was an insertion/duplication of 18bp. Mutations of the K-ras gene were detected in 26.7% (8/30) of AAH, 16.7% (5/30) of BAC and 10% (3/30) of invasive adenocarcinoma. None of the tumors with EGFR mutations had K-ras mutation simultaneously. Patients who had invasive adenocarcinoma with EGFR mutations were younger than those without mutations (60.6 versus 67.4 years, p=0.03). These results suggest that tumors with EGFR mutations may progress more rapidly and develop into invasive cancer faster than those without mutations. Alternatively it is also possible that some invasive adenocarcinomas with EGFR mutations may not follow the AAH-adenocarcinoma sequence. We analyzed 24 patients with multiple lung lesions and 13 patients had at least one lesion that had either an EGFR or K-ras mutation. In all cases each lesion had a different mutation status. This finding suggests that the genetic alterations responsible for the development of lung adenocarcinoma occur randomly even under exposure to the same carcinogen.

EGFR Mutations in Non-Small Cell Lung Carcinomas May Predict Response to Gefitinib

Studies have shown that epidermal growth factor receptor (EGFR) signaling is important to normal cell development and neoplastic transformation. EGFR inhibition has been shown to reduce cancer cell proliferation. Gefitinib, an EGFR tyrosine kinase inhibitor, has been shown to be effective in a subset of patients with chemotherapy-refractory non-small cell lung cancer (NSCLC), but there appears to be no accurate indicator that predicts patient sensitivity to this particular therapeutic agent. Two recent studies have identified somatic EGFR mutations in NSCLC that confer sensitivity to gefitinib in vitro and correlate strongly with patients' clinical response to the inhibitor.