Novel RNA variants in colorectal cancers

Abstract

With an annual estimated incidence of 1.4 million, and a five-year survival rate of 60%, colorectal cancer (CRC) is a major clinical burden. To identify novel RNA variants in CRC, we analyzed exon-level microarray expression data from a cohort of 202 CRCs. We nominated 25 genes with increased expression of their 3′ parts in at least one cancer sample each. To efficiently investigate underlying transcript structures, we developed an approach using rapid amplification of cDNA ends followed by high throughput sequencing (RACE-seq). RACE products from the targeted genes in 23 CRC samples were pooled together and sequenced. We identified VWA2-TCF7L2, DHX35-BPIFA2 and CASZ1-MASP2 as private fusion events, and novel transcript structures for 17 of the 23 other candidate genes. The high-throughput approach facilitated identification of CRC specific RNA variants. These include a recurrent read-through fusion transcript between KLK8 and KLK7, and a splice variant of S100A2. Both of these were overrepresented in CRC tissue and cell lines from external RNA-seq datasets.

Downregulation of castor zinc finger 1 predicts poor prognosis and facilitates hepatocellular carcinoma progression via MAPK/ERK signaling

“…Recently, the importance of CASZ1 in tumorigenesis is becoming increasingly recognized. Aberrant fusion transcript of CASZ1 has been reported in colorectal cancer [ 18 ] and bladder cancer [ 19 ]. CASZ1 is downregulated and functions as a crucial tumor suppressor in neuroblastoma [ 20 , 21 ].…”

CBX8 and CD96 Are Important Prognostic Biomarkers of Colorectal Cancer

“…Some potential biomarkers in cancers have been identified based on exon microarray or NGS. For example, through the combination of exon microarray and RNA sequencing (RNA-Seq), Hoff et al found that the fusion of VWA2-TCF7L2, DHX35-BPIFA2, and CASZ1-MASP2, as well as some novel transcript structures, may play an important role in CRC [ 13 ]. Compared with NGS, microarray has some obvious shortcomings, including the fact that it cannot detect unknown alterations of genomic structure that might contribute to progression of cancers [ 14 ].…”

Identification of CASZ1 NES reveals potential mechanisms for loss of CASZ1 tumor suppressor activity in neuroblastoma

“…A clinical case report showed that CASZ1 gene expression was disrupted as a consequence of human papillomavirus DNA integration into the CASZ1 gene locus in a case of cervical cancer (10). In colorectal cancer, CASZ1 and MASP2 fusion transcript was detected, and this fusion product encodes a N-terminal truncated MASP2 that under the control of CASZ1 promoter (11). Our studies have shown that the CASZ1 gene is silenced in poor prognosis neuroblastoma (NB) patient tumor samples through loss of heterozygosity and/or EZH2-mediated epigenetic silencing (12).…”