Clinical significance of DNA damage response factors and chromosomal instability in primary lung adenocarcinoma

Tatsuro Okamoto, Mikihiro Kohno, Kensaku Ito, Kazuki Takada, Masakazu Katsura, Yosuke Morodomi, Gouji Toyokawa, Fumihiro Shoji, Yoshihiko Maehara

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Aim: The purpose of this study was to investigate the biological role of DNA damage-response genes and chromosomal instability in primary lung adenocarcinoma. Materials and Methods: We investigated 60 surgically-resected lung adenocarcinomas. Levels of checkpoint kinase 2 gene (CHEK2) and breast cancer type 1 susceptibility protein gene (BRCA1) mRNA expression were evaluated by polymerase chain reaction (PCR). Epidermal growth factor receptor (EGFR) mutations (exon 19 deletion and exon 21 mutation) were detected by the PCR clamp method. Mutations in Kirsten rat sarcoma viral oncogene homolog gene (KRAS) and TP53 were examined by direct sequencing. Expression levels of p27 and p16 proteins were assessed by immunohistochemistry. Chromosomal aberrations (CA) were examined in 20 samples with single-nucleotide polymorphism-comparative genomic hybridization. Results: CHEK2 mRNA levels were significantly increased in tumor tissues compared to normal tissues (p=0.0123, paired t-test), whereas BRCA mRNA levels were not increased. TP53 mutation positivity and BRCA1 mRNA expression were positively associated with CHEK2 mRNA expression status (p=0.022 and p=0.0008). High CHEK2 mRNA expression was associated with poor recurrence-free survival (p=0.028). CHEK2 mRNA levels were higher in samples with a high CA frequency than in those with a low CA frequency (averages: 0.326 vs. 0.185; p=0.0129). Conclusion: The CHEK2 mRNA expression level was found elevated in lung adenocarcinoma and was related to a poor prognostic outcome. The CHEK2 pathway may be important for the proliferation of lung adenocarcinoma, especially in tumors with chromosomal instability.

Original languageEnglish
Pages (from-to)1729-1735
Number of pages7
JournalAnticancer research
Volume37
Issue number4
DOIs
Publication statusPublished - Apr 2017

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Checkpoint Kinase 2
Chromosomal Instability
DNA Damage
Messenger RNA
Chromosome Aberrations
Mutation
Genes
Gene Expression
Exons
BRCA1 Protein
BRCA1 Gene
Polymerase Chain Reaction
Comparative Genomic Hybridization
Adenocarcinoma of lung
p53 Genes
Oncogenes
Epidermal Growth Factor Receptor
Sarcoma
Single Nucleotide Polymorphism
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Okamoto, T., Kohno, M., Ito, K., Takada, K., Katsura, M., Morodomi, Y., ... Maehara, Y. (2017). Clinical significance of DNA damage response factors and chromosomal instability in primary lung adenocarcinoma. Anticancer research, 37(4), 1729-1735. https://doi.org/10.21873/anticanres.11505

Clinical significance of DNA damage response factors and chromosomal instability in primary lung adenocarcinoma. / Okamoto, Tatsuro; Kohno, Mikihiro; Ito, Kensaku; Takada, Kazuki; Katsura, Masakazu; Morodomi, Yosuke; Toyokawa, Gouji; Shoji, Fumihiro; Maehara, Yoshihiko.

In: Anticancer research, Vol. 37, No. 4, 04.2017, p. 1729-1735.

Research output: Contribution to journalArticle

Okamoto, T, Kohno, M, Ito, K, Takada, K, Katsura, M, Morodomi, Y, Toyokawa, G, Shoji, F & Maehara, Y 2017, 'Clinical significance of DNA damage response factors and chromosomal instability in primary lung adenocarcinoma', Anticancer research, vol. 37, no. 4, pp. 1729-1735. https://doi.org/10.21873/anticanres.11505
Okamoto, Tatsuro ; Kohno, Mikihiro ; Ito, Kensaku ; Takada, Kazuki ; Katsura, Masakazu ; Morodomi, Yosuke ; Toyokawa, Gouji ; Shoji, Fumihiro ; Maehara, Yoshihiko. / Clinical significance of DNA damage response factors and chromosomal instability in primary lung adenocarcinoma. In: Anticancer research. 2017 ; Vol. 37, No. 4. pp. 1729-1735.
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