Identification of novel mutations and functional impacts of EPAS1 in colorectal cancer

The novel findings of EPAS1 mutation in cancer tissues from colon cancer might be involved in carcinogenesis. Thus, the molecular and functional studies implied that EPAS1 plays crucial roles in CRC pathogenesis and have the potential to be used as a prognostic marker and as a therapeutic target. AbstractEndothelial PAS domain-containing protein 1 (EPAS1) has implications in many cancers. However, the molecular behaviours, functional roles and mutational status ofEPAS1 have never been studied in colorectal carcinoma (CRC). The study aims to examine the genetic alterations and functional roles ofEPAS1 in CRC. In addition, the clinical impacts ofEPAS1 in CRC were studied. SignificantEPAS1 DNA amplification (63.4%;n  =  52/82) and consequent mRNA overexpression (72%;n = 59/82) were noted in patients with CRC. In CRC, 16% (n = 13/82) of the patients had mutations in theEPAS1 coding sequence and most of the mutated samples exhibited aberrant DNA changes and mRNA overexpression. We have identified two novel variants, c.1084C>T; p.L362L and c.1121T>G; p.F374C in CRC. TheseEPAS1 aberrations in CRC were correlated with clinicopathological parameters, including tumour size, histological grade, T-stages, cancer perforation as well as the presence of synchronous cancer. Also, reduced cell proliferation, wound healing, migration and invasion were noted in colon cancer cells followed byEPAS1 silencing. To conclude, the results obtained from the current study indicated thatEPAS1...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research