Somatic Alterations of the Serine/Threonine KinaseLKB1Gene in Squamous Cell (SCC) and Large Cell (LCC) Lung Carcinoma

Autor:	Damjan Glavač, Mlakar, Mojca Strazisar, Rott T
Rok vydání:	2009
Předmět:	Adult Male Cancer Research Lung Neoplasms Somatic cell DNA Mutational Analysis Cell Adenocarcinoma Protein Serine-Threonine Kinases Biology Gene Expression Regulation Enzymologic Metastasis AMP-Activated Protein Kinase Kinases Carcinoma medicine Humans Gene Silencing Chromatography High Pressure Liquid Aged Aged 80 and over Serine/threonine-specific protein kinase Large cell Cancer Exons General Medicine Middle Aged medicine.disease Introns Gene Expression Regulation Neoplastic Genes ras medicine.anatomical_structure Oncology Cyclooxygenase 2 Case-Control Studies Mutation Carcinoma Squamous Cell Cancer research Carcinoma Large Cell Female
Zdroj:	Cancer Investigation. 27:407-416
ISSN:	1532-4192 0735-7907
DOI:	10.1080/07357900802427919
Popis:	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.
Databáze:	OpenAIRE
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