Identification of novel alternative splice variants of the BCL2L12 gene in human cancer cells using next-generation sequencing methodology. Issue 1 (1st April 2016)

• Record Type: Journal Article
• Authors: Adamopoulos, Panagiotis G.; Kontos, Christos K.; Tsiakanikas, Panagiotis; Scorilas, Andreas
• Is Part Of: Cancer letters. Volume 373:Issue 1(2016)
• Page Start: 119
• Page End: 129
• Publication Date: 2016-04-01
• Subjects: BCL2 family -- Splice variants -- Alternative splicing -- Apoptosis -- NGS; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.01.019
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: Using NGS, novel alternative splicing events of the BCL2L12 gene were uncovered. 50 novel transcript variants of the BCL2L12 gene were discovered. 11 novel transcripts of BCL2L12 are predicted to encode new protein isoforms. The other 39 splice variants are nonsense-mediated mRNA decay (NMD) candidates. Abstract: The next-generation sequencing (NGS) technology has enabled genome-wide studies, providing massively parallel DNA sequencing. NGS applications constitute a revolution in molecular biology and genetics and have already paved new ways in cancer research. BCL2L12 is an apoptosis-related gene, previously cloned from members of our research group. Like most members of the BCL2 gene family, it is highly implicated in various types of cancer and hematological malignancies. In the present study, we used NGS to discover novel alternatively spliced variants of the apoptosis-related BCL2L12 gene in many human cancer cell lines, after 3′-RACE nested PCR. Extensive computational analysis uncovered new alternative splicing events and patterns, resulting in novel alternative transcripts of the BCL2L12 gene. PCR was then performed to validate NGS data and identify the derived novel transcripts of the BCL2L12 gene. Therefore, 50 novel BCL2L12 splice variants were discovered. Since BCL2L12 is involved in the apoptotic machinery, the quantification of distinct BCL2L12 transcripts in human samples may have clinical applications in different types of cancer.