Missense Mutations in Exons 18–24 of EGFR in Hepatocellular Carcinoma Tissues

TL;DR

This study identifies various EGFR mutations in hepatocellular carcinoma tissues, but finds no clear link between these mutations and EGFR overexpression or other tumor characteristics.

Contribution

The study reports novel missense mutations in EGFR exons 18–24 in hepatocellular carcinoma, expanding the known mutation landscape in this cancer type.

Findings

EGFR overexpression was detected in 32.5% of hepatocellular carcinoma tissues.

Missense mutations in EGFR exons 18–24 were found in 39.4% of hepatocellular carcinoma tissues.

No significant association was found between EGFR mutations and clinical or pathological factors.

Abstract

Epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase receptor, plays important roles in various cancers. In nonsmall cell lung cancer (NSCLC), EGFR mutations cluster around the ATP-binding pocket (exons 18–21) and some of these mutations activate the kinase and induce an increased sensitivity to EGFR-tyrosine kinase inhibitors. Nevertheless, data of EGFR mutations in HCC are limited. In this study, we investigated EGFR expression by immunohistochemistry and EGFR mutations (exons 18–24) by PCR cloning and sequencing. EGFR overexpression in HCC and matched nontumor tissues were detected in 13/40 (32.5%) and 10/35 (28.6%), respectively. Moreover, missense and silent mutations were detected in 13/33 (39.4%) and 11/33 (33.3%) of HCC tissues, respectively. The thirteen different missense mutations were p.L730P, p.V742I, p.K757E, p.I780T, p.N808S, p.R831C, p.V851A, p.V897A, p.S912P, p.P937L, p.T940A, p.M947V, and p.M947T. We also found already known SNP, p.Q787Q (CAG>CAA), in 13/33 (39.4%) of HCC tissues. However, no significant association was detected between EGFR mutations and EGFR overexpression, tissue, age, sex, tumor size, AFP, HBsAg, TP53, and Ki-67. Further investigation is warranted to validate the frequency and activity of these missense mutations, as well as their roles in HCC tumorigenesis and in EGFR-targeted therapy.

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