Drug Discoveries & Therapeutics
Online ISSN : 1881-784X
Print ISSN : 1881-7831
ISSN-L : 1881-7831
Original Articles
LKB1, TP16, EGFR, and KRAS somatic mutations in lung adeno-carcinomas from a Chiba Prefecture, Japan cohort
Yoshio SuzukiTadahiro OonishiTakashi KudoHirofumi Doi
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2012 Volume 6 Issue 1 Pages 24-30


The discovery of somatic mutations in cancer-related genes has been applied to understand the genetic basis of cancer. Here we report somatic mutations of two tumor suppressor genes: LKB1 (exons 1, 4, and 8) and TP16 (CDKN2A) (exons 1 and 2); and two oncogenes: epidermal growth factor receptor EGFR (exons 18-21) and KRAS (exon 2) in 97 lung adenocarcinoma tissues in a cohort from the Kujukuri coast area of Chiba, Japan. In the LKB1 gene, only F354L substitutions were observed in 14 of the 97 tissue samples (14.4%). In the TP16 gene, only two deletions were observed in contrast to previous reports. On the other hand, the EGFR gene was highly mutated (38.1%) and mainly L858R substitutions occurred (23.7%) as well as insertions and deletions. In the KRAS gene, 10 substitutions at codon 12 were observed (10.3%). Co-occurrence of EGFR and KRAS somatic mutations was identified in one patient, those of EGFR and LKB1 were in three patients, and those of KRAS and LKB1 were in four patients. The lower rates of LKB1, TP16, and KRAS somatic mutations in lung adenocarcinomas are characteristic of the Kujukuri cohort as compared to Caucasians. while being infrequent in NSCLC Another review (were observed in 20.18% of lung adenocarcinoma byanalyzing the Catalog of Somatic Mutations in Cancer(COSMIC) (the W(CDKN2Aa tumor suppressor gene and has been reported to show a high rate of deletions as a major type of somatic mutation in cancerin the COSMIC database (suppressor genes, central role in tumorigenesis. EGFR phosphorylates tyrosine residues of tarincluding KRAS, to initiate multiple signaling pathwaysresulting in cell proliferation, migration, metastasis,resistance to apoptosis, and angiogenesis (molecule inhibitors of EGFR tyrosine kinase activity (TKIs) such as gefitinib and erlotinib provide a good concept for anticancer drugs. Howeversignificant variability in the EGFR

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© 2012 International Research and Cooperation Association for Bio & Socio-Sciences Advancement
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