Novel RNA variants in colorectal cancers

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 expres...

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Main Authors: Hoff, Andreas M., Johannessen, Bjarne, Alagaratnam, Sharmini, Zhao, Sen, Nome, Torfinn, Løvf, Marthe, Bakken, Anne C., Hektoen, Merete, Sveen, Anita, Lothe, Ragnhild A., Skotheim, Rolf I.
Format: Online
Language:English
Published: Impact Journals LLC 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742197/
id pubmed-4742197
recordtype oai_dc
spelling pubmed-47421972016-04-04 Novel RNA variants in colorectal cancers Hoff, Andreas M. Johannessen, Bjarne Alagaratnam, Sharmini Zhao, Sen Nome, Torfinn Løvf, Marthe Bakken, Anne C. Hektoen, Merete Sveen, Anita Lothe, Ragnhild A. Skotheim, Rolf I. Research Paper 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. Impact Journals LLC 2015-10-12 /pmc/articles/PMC4742197/ /pubmed/26474385 Text en Copyright: © 2015 Hoff et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Hoff, Andreas M.
Johannessen, Bjarne
Alagaratnam, Sharmini
Zhao, Sen
Nome, Torfinn
Løvf, Marthe
Bakken, Anne C.
Hektoen, Merete
Sveen, Anita
Lothe, Ragnhild A.
Skotheim, Rolf I.
spellingShingle Hoff, Andreas M.
Johannessen, Bjarne
Alagaratnam, Sharmini
Zhao, Sen
Nome, Torfinn
Løvf, Marthe
Bakken, Anne C.
Hektoen, Merete
Sveen, Anita
Lothe, Ragnhild A.
Skotheim, Rolf I.
Novel RNA variants in colorectal cancers
author_facet Hoff, Andreas M.
Johannessen, Bjarne
Alagaratnam, Sharmini
Zhao, Sen
Nome, Torfinn
Løvf, Marthe
Bakken, Anne C.
Hektoen, Merete
Sveen, Anita
Lothe, Ragnhild A.
Skotheim, Rolf I.
author_sort Hoff, Andreas M.
title Novel RNA variants in colorectal cancers
title_short Novel RNA variants in colorectal cancers
title_full Novel RNA variants in colorectal cancers
title_fullStr Novel RNA variants in colorectal cancers
title_full_unstemmed Novel RNA variants in colorectal cancers
title_sort novel rna variants in colorectal cancers
description 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.
publisher Impact Journals LLC
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742197/
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