Somatically acquired mutations in the epidermal growth factor receptor (EGFR) gene in lung cancer are associated with significant clinical responses to gefitinib, a tyrosine kinase inhibitor that targets EGFR. We screened the EGFR in 469 resected tumours of patients with lung cancer, which included 322 adenocarcinomas, 102 squamous cell carcinomas, 27 large cell carcinomas, 13 small cell carcinomas, and five other cell types. PCR with a specific condition was performed to identify any deletion in exon 19, while mutantallele-specific amplification was performed to identify a mutation in codon 858 of exon 21. EGFR mutations were found in 136 cases (42.2%) with adenocarcinoma, in one case with large cell carcinoma, and in one case with pleomorphic carcinoma. An in-frame deletion in exon 19 was found in 62 cases while an L858R mutation was found in 77 cases. In the 322 cases with adenocarcinoma, these mutations were more frequently found in women than in men (P ¼ 0.0004), in well differentiated tumours than in poorly differentiated tumours (P ¼ 0.0014), and in patients who were never smokers than in patients who were current/former smokers (Po0.0001). The mutation was more frequently observed in patients who smoked p20 pack-year, and in patients who quit at least 20 years before the date of diagnosis for lung cancer. The K-ras mutations were more frequently found in smokers than in never smokers, and in high-dose smokers than in low-dose smokers. In conclusion, the mutations within the tyrosine kinase domain of EGFR were found to specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking.

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Contrary to widely held beliefs, the gene encoding proteolipid protein (PLP), the major structural protein of central nervous system myelin, is expressed in Schwann cells and their tumors. Proteolipid mRNA was identified in human acoustic neuromas and in rat and rabbit sciatic nerves using a human PLP cDNA as a probe. Proteolipid protein itself was shown to be present in human and rat sciatic nerve Schwann cells by immunofluorescence microscopy and by Western blot analysis using antisera raised to a synthetic PLP polypeptide. Although easily detected in the Schwann cell body, PLP was not detected in the peripheral myelin itself, suggesting that the PLP is preferentially excluded from this portion of the Schwann cell membrane.

Activation of the Wnt-signaling pathway is known to play a crucial role in carcinogenesis of various human organs including the colon, liver, prostate, and endometrium. To investigate the mechanisms underlying hepatocellular carcinogenesis, we attempted to identify genes regulated by beta-catenin/Tcf complex in a human hepatoma cell line, HepG2, in which an activated form of beta-catenin is expressed. By means of cDNA microarray, we isolated a novel human gene, termed MARKL1 (MAP/microtubule affinity-regulating kinase-like 1), whose expression was downregulated in response to decreased Tcf/LEF1 activity. The transcript expressed in liver consisted of 3529 nucleotides that contained an open reading frame of 2256 nucleotides, encoding 752 amino acids homologous to human MARK3 (MAP/microtubule affinity-regulating kinase 3). Expression levels of MARKL1 were markedly elevated in eight of nine HCCs in which nuclear accumulation of beta-catenin were observed, which may suggest that MARKL1 plays some role in hepatocellular carcinogenesis.

The occurrence of MET amplification and EGFR/ K-ras mutations might be mutually exclusive suggesting several distinct mechanisms in the development of lung adenocarcinoma. The wild type of K-ras, negative p-MET 1234/1235, and positive expression of HGF may be a useful marker for predicting poor prognosis of patients who underwent surgical resection of lung adenocarcinoma.