LKB1 gene alterations in surgically resectable adenocarcinoma of the lung.

PURPOSE: Germline mutations of LKB1 (also known as SKT11; locus 19p13.3) cause the occurrence of autosomal dominant Peutz-Jeghers syndrome (PJS). Nearly half of the non-small cell lung cancer (NSCLC) cell lines and one-third of lung adenocarcinoma in Caucasian patients have an LKB1 mutation. METHODS: This study examined the mutational hot spots of the LKB1 gene in surgical resectable lung adenocarcinoma. Exons 1, 6, and 7 of the LKB1 gene were sequenced in 174 Japanese patients with lung adenocarcinoma (including 157 men and 17 women). RESULTS: Only five patients had LKB1 gene alterations (2.9%). All of them were male smokers, and no LKB1 mutation was observed in any of the females. The details of LKB1 alterations were: one 5 bp deletion in intron 5, one Gly to Phe substitution at codon 279 of exon 6, and three Pro to Leu substitutions at codon 281 of exon 6. The P281L alteration and 5 bp deletion in the intron 5 were found to be germline polymorphisms. The G279F was confirmed to be a novel somatic mutation. None of the five patients with an LKB1 alteration showed either an EGFR or K-ras mutation. CONCLUSION: The LKB1 gene alteration is rare in Japanese patients with lung adenocarcinoma, and is generally limited to male smokers.