Identification of a novel gene fusion RNF213-SLC26A11 in chronic myeloid leukemia by RNA-Seq

Abstract

Chronic myeloid leukemia (CML) was the first hematological malignancy to be associated with a specific genetic lesion. The Philadelphia translocation, producing a BCR‑ABL hybrid oncogene, is the most common mechanism of CML development. However, in the present study, b3a2, b2a2 and ela2 fusion junctions of the breakpoint cluster region (BCR)-V-abl Abelson murine leukemia viral oncogene homolog 1 (ABL) gene were not detected in patients diagnosed with CML three and four years previously. RNA-Seq technology, with an average coverage of ~30‑fold, was used to detect gene fusion events in a patient with a 6-year history of CML, identified to be in the chronic phase of the disease. Using deFuse and TopHat‑fusion programs with improved filtering methods, we identified two reliable gene fusions in a blood sample obtained from the CML patient, including extremely low expression levels of the classic BCR‑ABL1 gene fusion. In addition, a novel gene fusion involving the ring finger protein 213 (RNF213)-solute carrier family 26, member 11 (SLC26A11) was identified and validated by reverse transcription polymerase chain reaction. Further bioinformatic analysis revealed that specific domains of SLC26A11 were damaged, which may affect the function of sulfate transportation of the normal gene. The present study demonstrated that, in specific cases, alternative gene fusions, besides BCR‑ABL, may be associated with the development of CML.

Lipidomic fatty acid profile and global gene expression pattern in mammary gland of rats that were exposed to lard-based high fat diet during fetal and lactation periods associated to breast cancer risk in adulthood

“…Rnf213 and Htr3b were both downregulated in the GL group. Rnf213 encodes a protein with ring finger domain and it is involved in chromosomal arrangement with c-Myc and ALK in anaplastic large cell lymphoma, and with SLC26A11 in chronic myeloid leukemia [48][49][50].…”

RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas

“…The RNF213-SLC26A11 fusion transcript was found in a chronic myeloid leukemia patient (Zhou et al 2013). The FGFR3-TACC3 fusion transcript was initially reported by Singh et al (2012) as a recurrent fusion transcript in GBMs.…”

“…1C). The RNF213-SLC26A11 fusion transcript was previously identified in a chronic myeloid leukemia specimen (Zhou et al 2013). This fusion transcript was detected in one pGBM (one of 59 or 1.7%) and a recurrent grade III glioma (one of 13, or 7.7%) (Supplemental Fig.…”

Understanding next generation sequencing in oncology: A guide for oncologists

“…As NGS uses DNA, this requires reverse transcription of the RNA to cDNA prior to sequencing (Wang et al, 2009). RNA-Seq provides information on the expression level (amount of RNA) of the RNA sequences and novel splice isoforms and can also detect gene fusions (Carrara et al, 2013;Edgren et al, 2011;Zhou et al, 2013).…”