Hypomethylation and increased expression of the putative oncogene ELMO3 are associated with lung cancer development and metastases formation
Signe Søes1, Iben Lyster Daugaard1, Brita Singers Sørensen2, Andreas Carus2, Manuel Mattheisen1, Jan Alsner2, Jens Overgaard2, Henrik Hager3, Lise Lotte Hansen1, Lasse Sommer Kristensen1,4
1 Department of Biomedicine, University of Aarhus, Aarhus C, Denmark
2 Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus C, Denmark
3 Department of Pathology, Aarhus University Hospital, Aarhus C, Denmark
4 Department of Hematology, Rigshospitalet, Copenhagen, Denmark
Correspondence:
Lasse Sommer Kristensen, email:
Keywords: Non-Small Cell Lung Cancer, metastases, DNA methylation, oncogenes, microRNA
Received: March 05, 2014 Accepted: May 23, 2014 Published: May 23, 2014
Abstract
Numerous genetic and epigenetic events driving tumorigenesis have been characterized. However, knowledge is lacking on the particular events required for the metastatic spread of cancer cells. The engulfment and cell motility 3 (ELMO3) gene plays an important role for the migratory potential of cells, but have not previously been studied in primary samples from cancer patients. We collected material from primary non-small cell lung cancer (NSCLC) tumors and paired brain or adrenal gland metastases from 26 patients and from 26 primary tumor samples from metastasis-free patients matched for age, gender, histology, T-stage, smoking status, and proportion of tumor cells. Using reverse transcriptase–quantitative PCR (RT-qPCR) ELMO3 was shown to be overexpressed in primary tumors from patients with distant metastases compared to normal lung tissue (p<0.001), and compared to primary tumors from metastasis-free patients (p<0.001). The increased expression coincided with decreased methylation levels of the ELMO3 promoter region. High expression and hypomethylation of ELMO3 were also observed when studying the paired brain and adrenal gland metastases. In conclusion, the putative oncogene, ELMO3, is overexpressed in NSCLC in combination with hypomethylation of its promoter and these cancer-specific events are associated with the formation of metastases.
