In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 2897-2897
Abstract:
Genes that are frequently deregulated in cancer are clinically attractive as both potential pan-cancer diagnostic markers and therapeutic targets. Here we compared Cap Analysis of Gene Expression (CAGE) profiles from 225 cancer cell lines and 339 corresponding primary cell samples to identify transcripts that are recurrently deregulated in a broad range of cancer types. CAGE is a 5’ sequence tag technology that globally determines transcription start sites (TSS) in the genome and their expression levels. This allowed us to assess novel aspects of the cancer transcriptome. First, we identified (at promoter resolution) hundreds of protein coding and long non-coding transcripts that are commonly de-regulated in cancer cell lines. Next, we showed that promoters that overlap repetitive elements (especially SINE/Alu and LTR/ERV1 elements) are often upregulated in cancer. In particular, a specific repeat family, REP522 (largely palindromic, unclassified interspersed repeat of ∼1.8Kb in size), was strongly enriched for the most up-regulated promoters. To our knowledge this is the first report implicating REP522 activation in cancer. Then, taking advantage of the fact that CAGE data can be used to estimate the activity of enhancers from balanced bidirectional transcription we identified 90 enhancer RNA producing regions that are recurrently activated in cancer cell lines. With ENCODE ChIA-PET data, we linked 16 of the cancer-activated enhancers to promoters of known cancer related genes. Finally, to confirm that our results are relevant to clinical tumors we performed complementary analysis in RNA-seq data from 4,055 tumors and 563 normal tissues profiled by The Cancer Genome Atlas (TCGA) and we identified a core set of pan-cancer biomarkers (of both coding and non-coding transcripts) that are recurrently perturbed in both the FANTOM5 and TCGA datasets. In summary, our extensive transcriptome analysis identified a comprehensive set of candidate biomarkers with pan-cancer potential, and extended the perspective of enhancers and repetitive elements that are recurrently activated during carcinogenesis. Citation Format: Bogumil Kaczkowski, Yuji Tanaka, Hideya Kawaji, Albin Sandelin, Robin Andersson, Masayoshi Itoh, Timo Lassmann, Yoshihide Hayashizaki, Piero Carninci, Alistair R.R. Forrest, FANTOM5 Consortium. Recurrent transcriptome alterations across multiple cancer types. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2897.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2016-2897
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2016
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
Bookmarklink