Detection of EGFR- and HER2-activating mutations in squamous cell carcinoma involving the head and neck

Abstract

Recent reports have indicated that mutations in the epidermal growth factor receptor-1 (EGFR) occur in about 7% of patients with squamous cell carcinoma of the head and neck. It is known that many patients with nonsmall-cell lung cancer who respond to the EGFR inhibitors gefitinib and erlotinib have tumors with EGFRactivating mutations. This might suggest that patients with head and neck squamous carcinoma, who also have tumors with EGFR-activating mutations, might represent a patient population who could benefit from gefitinib or erlotinib therapy. High-resolution melting amplicon analysis (HRMAA) is a recently described technique which can be used for screening tumor DNA isolated from paraffin blocks for tyrosine kinase-activating mutations. In this report we screened 24 cases of squamous cell carcinoma, either primary in the head and neck or secondarily involving the head and neck area, for activating mutations in EGFR exons 18, 19, 20, 21, and for HER2 exons 19 and 20. All cases were followed up by direct DNA sequencing. Two (8%) of the 24 cases were positive. One case was a maxillary sinus tumor which contained an exon 20-activating mutation (N771YinsG). Surprisingly, the other case was a primary squamous cell carcinoma of the skin which invaded the head and neck area only secondarily. This tumor contained an exon 19-activating mutation (G729E). No HER2-activating mutations were found. The presence of a small number of squamous cell carcinomas in the head and neck area with EGFR-activating mutations suggests the existence of a population of patients who could derive benefit from gefitinib or erlotinib therapy. HRMAA could serve as a screening method to easily and rapidly identify these patients.

Prognostic Significance of Epidermal Growth Factor Receptor Phosphorylation and Mutation in Head and Neck Squamous Cell Carcinoma

“…In NSCLC, some mutations dramatically respond to treatment with EGFR inhibitors and have various levels of sensitivity to treatment [2,3]. In contrast to NSCLC, there are only a few reports regarding EGFR mutations of exon 19 and 20 in HNSCC [15][16][17], where active sites for tyrosine phosphorylation exist. Somatic mutations in active sites of EGFR are consistent with our results, although the positions of the mutations were not the same.…”

Validation of High-Resolution DNA Melting Analysis for Mutation Scanning of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Gene

“…10, No. 5 already been successfully applied to the analysis of TP53, 22 phenylalanine hydroxylase gene, 23 factor VIII, 24 factor II, factor V, HFE, 11,25,26 C-kit, 27 EGFR HER2, 28 RET, 29 and CFTR. 30 In this last study, the authors report the CFTR scanning by HRM after PCR amplification of 37 exon/intron fragments in 2 panels of 96 random white UK blood donors and 30 blinded DNA samples enriched for CF-causing variants.…”

Detection of c-kit exons 11- and 17-activating mutations in testicular seminomas by high-resolution melting amplicon analysis

“…19 Several previous studies indicate that a normal melting curve obtained by high-resolution melting amplicon analysis on PCRamplified products reflects an underlying normal DNA sequence. [19][20][21] In screening for exon 17 mutations, all cases were followed up by direct bidirectional DNA sequencing. All normal melting curves were found to be the result of normal DNA sequences and all abnormal curves were found to be the result of underlying mutations.…”