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DDR2 polymorphisms and mRNA expression in lung cancers of Japanese patients
Hidefumi Sasaki1, Masayuki Shitara, Keisuke Yokota
1Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Abstract:
Discoidin domain receptor 2, DDR2, is a tyrosine kinase receptor for fibrillar collagen that is involved in postnatal development, tissue repair and primary and metastatic cancer progression. Recently, mutations in the DDR2 kinase gene were identified in squamous cell lung cancer from large-scale Sanger sequencing. The present study investigated the DDR2 gene mutations and mRNA expression in surgically treated non-small cell lung cancer (NSCLC) of squamous histology cases. The presence or absence of DDR2 mutations at the kinase and discoidin domain was analyzed by direct sequencing. In this cohort, DDR2 mutations were not observed in the 166 patients with lung cancer, although DDR2 polymorphisms were observed (H136H, n=14) at the discoidin domain. mRNA levels of DDR2 in lung tumor samples and the adjacent normal lung samples were simultaneously analyzed. DDR2 mRNA levels were significantly decreased in tumor samples compared with normal lung samples. However, the DDR2 mRNA levels were elevated in the DDR2 polymorphism cases.
Insights
Discoidin domain receptor 2 (DDR2) mutations were not found in this non-small cell lung cancer cohort. However, DDR2 mRNA levels were significantly decreased in tumors, but elevated in cases with DDR2 polymorphisms.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Discoidin domain receptor 2 (DDR2) is a tyrosine kinase receptor implicated in cancer progression.
- Recent studies identified DDR2 kinase gene mutations in squamous cell lung cancer.
Purpose of the Study:
- To investigate DDR2 gene mutations and mRNA expression in surgically treated non-small cell lung cancer (NSCLC) of squamous histology.
- To analyze DDR2 mutations in kinase and discoidin domains and assess mRNA expression levels in tumor versus normal lung tissue.
Main Methods:
- Direct sequencing was used to analyze DDR2 gene mutations in the kinase and discoidin domains.
- mRNA levels of DDR2 were analyzed in lung tumor samples and adjacent normal lung samples.
Main Results:
- No DDR2 mutations were observed in 166 NSCLC patients.
- DDR2 polymorphisms (H136H) were identified in 14 cases.
- DDR2 mRNA levels were significantly decreased in tumor samples compared to normal lung samples.
- DDR2 mRNA levels were elevated in patients with DDR2 polymorphisms.
Conclusions:
- DDR2 mutations are not prevalent in this cohort of surgically treated NSCLC.
- DDR2 mRNA expression is downregulated in NSCLC tumors.
- DDR2 polymorphisms may influence DDR2 mRNA levels in lung cancer.
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