Transcriptome analysis of recurrently deregulated genes across multiple cancers identifies new pan-cancer biomarkers

Bogumil Kaczkowski; Yuji Tanaka; Hideya Kawaji; Albin Gustav Sandelin; Robin Andersson; Masayoshi Itoh; Timo Lassmann; null the FANTOM5 consortium; Yoshihide Hayashizaki; Piero Carninci; Alistair R. R. Forrest

doi:10.1158/0008-5472.can-15-0484

Transcriptome analysis of recurrently deregulated genes across multiple cancers identifies new pan-cancer biomarkers

Bogumil Kaczkowski, Yuji Tanaka, Hideya Kawaji, Albin Gustav Sandelin, Robin Andersson, Masayoshi Itoh, Timo Lassmann, the FANTOM5 consortium, Yoshihide Hayashizaki, Piero Carninci, Alistair R. R. Forrest

Computational and RNA Biology

44 Citations (Scopus)

Abstract

Genes that are commonly deregulated in cancer are clinically attractive as candidate pan-diagnostic markers and therapeutic targets. To globally identify such targets, we compared Cap Analysis of Gene Expression profiles from 225 different cancer cell lines and 339 corresponding primary cell samples to identify transcripts that are deregulated recurrently in a broad range of cancer types. Comparing RNA-seq data from 4,055 tumors and 563 normal tissues profiled in the The Cancer Genome Atlas and FANTOM5 datasets, we identified a core transcript set with theranostic potential. Our analyses also revealed enhancer RNAs, which are upregulated in cancer, defining promoters that overlap with repetitive elements (especially SINE/Alu and LTR/ERV1 elements) that are often upregulated in cancer. Lastly, we documented for the first time upregulation of multiple copies of the REP522 interspersed repeat in cancer. Overall, our genomewide expression profiling approach identified a comprehensive set of candidate biomarkers with pan-cancer potential, and extended the perspective and pathogenic significance of repetitive elements that are frequently activated during cancer progression.

Original language	English
Journal	Cancer Research
Volume	76
Issue number	2
Pages (from-to)	216-226
ISSN	0008-5472
DOIs	https://doi.org/10.1158/0008-5472.can-15-0484
Publication status	Published - 15 Jan 2016

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Kaczkowski, B., Tanaka, Y., Kawaji, H., Sandelin, A. G., Andersson, R., Itoh, M., Lassmann, T., the FANTOM5 consortium, Hayashizaki, Y., Carninci, P., & Forrest, A. R. R. (2016). Transcriptome analysis of recurrently deregulated genes across multiple cancers identifies new pan-cancer biomarkers. Cancer Research, 76(2), 216-226. https://doi.org/10.1158/0008-5472.can-15-0484

Kaczkowski, B, Tanaka, Y, Kawaji, H, Sandelin, AG , Andersson, R, Itoh, M, Lassmann, T, the FANTOM5 consortium, Hayashizaki, Y, Carninci, P & Forrest, ARR 2016, 'Transcriptome analysis of recurrently deregulated genes across multiple cancers identifies new pan-cancer biomarkers', Cancer Research, vol. 76, no. 2, pp. 216-226. https://doi.org/10.1158/0008-5472.can-15-0484

@article{b5167b617195402a904ce799c8dfca23,

title = "Transcriptome analysis of recurrently deregulated genes across multiple cancers identifies new pan-cancer biomarkers",

abstract = "Genes that are commonly deregulated in cancer are clinically attractive as candidate pan-diagnostic markers and therapeutic targets. To globally identify such targets, we compared Cap Analysis of Gene Expression profiles from 225 different cancer cell lines and 339 corresponding primary cell samples to identify transcripts that are deregulated recurrently in a broad range of cancer types. Comparing RNA-seq data from 4,055 tumors and 563 normal tissues profiled in the The Cancer Genome Atlas and FANTOM5 datasets, we identified a core transcript set with theranostic potential. Our analyses also revealed enhancer RNAs, which are upregulated in cancer, defining promoters that overlap with repetitive elements (especially SINE/Alu and LTR/ERV1 elements) that are often upregulated in cancer. Lastly, we documented for the first time upregulation of multiple copies of the REP522 interspersed repeat in cancer. Overall, our genomewide expression profiling approach identified a comprehensive set of candidate biomarkers with pan-cancer potential, and extended the perspective and pathogenic significance of repetitive elements that are frequently activated during cancer progression.",

author = "Bogumil Kaczkowski and Yuji Tanaka and Hideya Kawaji and Sandelin, {Albin Gustav} and Robin Andersson and Masayoshi Itoh and Timo Lassmann and {the FANTOM5 consortium} and Yoshihide Hayashizaki and Piero Carninci and Forrest, {Alistair R. R.}",

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doi = "10.1158/0008-5472.can-15-0484",

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AU - Kaczkowski, Bogumil

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AU - Kawaji, Hideya

AU - Sandelin, Albin Gustav

AU - Andersson, Robin

AU - Itoh, Masayoshi

AU - Lassmann, Timo

AU - the FANTOM5 consortium, null

AU - Hayashizaki, Yoshihide

AU - Carninci, Piero

AU - Forrest, Alistair R. R.

PY - 2016/1/15

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N2 - Genes that are commonly deregulated in cancer are clinically attractive as candidate pan-diagnostic markers and therapeutic targets. To globally identify such targets, we compared Cap Analysis of Gene Expression profiles from 225 different cancer cell lines and 339 corresponding primary cell samples to identify transcripts that are deregulated recurrently in a broad range of cancer types. Comparing RNA-seq data from 4,055 tumors and 563 normal tissues profiled in the The Cancer Genome Atlas and FANTOM5 datasets, we identified a core transcript set with theranostic potential. Our analyses also revealed enhancer RNAs, which are upregulated in cancer, defining promoters that overlap with repetitive elements (especially SINE/Alu and LTR/ERV1 elements) that are often upregulated in cancer. Lastly, we documented for the first time upregulation of multiple copies of the REP522 interspersed repeat in cancer. Overall, our genomewide expression profiling approach identified a comprehensive set of candidate biomarkers with pan-cancer potential, and extended the perspective and pathogenic significance of repetitive elements that are frequently activated during cancer progression.

AB - Genes that are commonly deregulated in cancer are clinically attractive as candidate pan-diagnostic markers and therapeutic targets. To globally identify such targets, we compared Cap Analysis of Gene Expression profiles from 225 different cancer cell lines and 339 corresponding primary cell samples to identify transcripts that are deregulated recurrently in a broad range of cancer types. Comparing RNA-seq data from 4,055 tumors and 563 normal tissues profiled in the The Cancer Genome Atlas and FANTOM5 datasets, we identified a core transcript set with theranostic potential. Our analyses also revealed enhancer RNAs, which are upregulated in cancer, defining promoters that overlap with repetitive elements (especially SINE/Alu and LTR/ERV1 elements) that are often upregulated in cancer. Lastly, we documented for the first time upregulation of multiple copies of the REP522 interspersed repeat in cancer. Overall, our genomewide expression profiling approach identified a comprehensive set of candidate biomarkers with pan-cancer potential, and extended the perspective and pathogenic significance of repetitive elements that are frequently activated during cancer progression.

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JO - Cancer Research

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Transcriptome analysis of recurrently deregulated genes across multiple cancers identifies new pan-cancer biomarkers

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