Somatic Alterations of the Serine/Threonine Kinase LKB1 Gene in Squamous Cell (SCC) and Large Cell (LCC) Lung Carcinoma

Abstract

Somatic LKB1 serine/threonine kinase alterations are rare in sporadic cancers, with the exception lung adenocarcinoma, but no mutations in squamous cell or large cell primary carcinoma were discovered. We screened the LKB1 gene in 129 primary nonsmall cell lung carcinomas, adjacent healthy lung tissue, and control blood samples. Forty-five percent of nonsmall cell lung tumors harbored either intron or exon alterations. We identified R86G, F354L, Y272Y and three polymorphisms: 290+36G/T, 386+156G/T, and 862+145C/T (novel). R86G (novel) and F354L mutations were found in six squamous cell carcinomas and three large cell cancer carcinomas, but not in the adjacent healthy tissue or controls samples. The F354L mutation was found in advanced squamous cell carcinomas with elevated COX-2 expression, rare P53, and no K-RAS mutation. Results indicate that the LKB1 gene is changed in a certain proportion of nonsmall cell lung tumors, predominately in advanced squamous lung carcinoma. Inactivation of the gene takes place via the C-terminal domain and could be related to mechanisms influencing tumor initiation, differentiation, and metastasis.

Keywords:

• LKB1
• SCC
• LCC
• Mutation detection
• P53
• K-RAS
• DHPLC
• COX-2