Article citationsMore>>

Kuramochi, M., Fukuhara, H., Nobukuni, T., Kanbe, T., Maruyama, T., Ghosh, H.P., Pletcher, M., Isomura, M., Onizuka, M., Kitamura, T., Sekiya, T., Reeves, R.H. and Murakami, Y. (2001) TSLC1 Is a Tumor-Suppressor Gene in Human Non-Small-Cell Lung Cancer. Nature Genetics, 27, 427-430.
http://dx.doi.org/10.1038/86934

has been cited by the following article:

• TITLE: Promoter Methylation of the CADM1 and 4.1B Genes Occurs Independently of the EGFR or the KRAS2 Mutation in Non-Small Cell Lung Cancer

  AUTHORS: Hiroyuki Kogai, Shinji Kikuchi, Takashi Obana, Yumi Tsuboi, Tomoko Maruyama, Mika Sakurai-Yageta, Hisao Asamura, Yae Kanai, Yoshinori Murakami

  KEYWORDS: Non-Small Cell Lung Cancer, EGFR Mutation, KRAS Mutation, CADM1 Methylation, 4.1B Methylation

  JOURNAL NAME: Journal of Cancer Therapy, Vol.6 No.3, March 17, 2015

  ABSTRACT: Objective: Targeting mutated EGFR by EGFR-tyrosine kinase inhibitors (EGFR-TKI) is a potent approach to a subset of non-small cell lung cancer (NSCLC). However, the response to EGFR-TKI varies in individual cases even among tumors carrying the sameEGFRmutation, suggesting the involvement of modifying factors. To characterize possible modifiers, we examined mutation state of theEGFRand theKRASgenes in Japanese NSCLC and compared them with the methylation state of lung tumor suppressors, theCADM1 and4.1B,whose products have potentials to modify the functions of EGFR or KRAS. Materials and methods: A total of 103 Japanese NSCLC and 11 NSCLC cell lines were examined. Genomic DNA of exons 18–21 of theEGFRand exons 1 and 2 of theKRASwere amplified by polymerase chain reaction (PCR), followed by single-strand conformation polymorphism analysis and direct sequencing. Methylation status of gene promoters in NSCLC cells were examined by methylation-specific PCR. Results: Mutations of theEGFRandKRASwere detected mutually exclusively in 27 and 11 out of 103 NSCLC cases, respectively.EGFRmutations were observed exclusively in adenocarcinoma (27 of 69, 41%) and preferentially in tumors from female and non-smokers (p EGFRand 4 (36%) and 8 (73%) of 11 tumors carrying mutatedKRASshowed methylation of theCADM1 and 4.1B, respectively.EGFR-mutated tumors with methylation of eitherCADM1 or 4.1Bshowed more malignant features than those with unmethylatedCADM1 and 4.1B(p CADM1 and4.1Bare independent of the mutation status of theEGFRorKRASbut play roles in the malignant progression of NSCLC. Integration of epigenetic information would be useful for identifying possible modifiers to predict the response or recurrence of lung adenocarcinoma to the EGFR-TKI therapy.