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Open AccessArticle

Pan-Cancer Mutational and Transcriptional Analysis of the Integrator Complex

Institute of Genetics and Biophysics “Adriano Buzzati Traverso”, CNR, 80131 Naples, Italy
Department of Science and Technology, University of Naples “Parthenope”, 80143 Naples, Italy
Department of Environmental, Biological, and Pharmaceutical Sciences and Technologies, University of Campania “Luigi Vanvitelli”, 81100 Caserta, Italy
Department of Biochemistry, Biophysics and General Pathology, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio, 80138 Naples, Italy
Author to whom correspondence should be addressed.
These two authors contributed equally to this work as co-last authors.
Academic Editor: Sabrina Angelini
Int. J. Mol. Sci. 2017, 18(5), 936;
Received: 10 April 2017 / Revised: 20 April 2017 / Accepted: 23 April 2017 / Published: 29 April 2017
(This article belongs to the Special Issue Transcriptome Profiling in Human Diseases)
PDF [4074 KB, uploaded 29 April 2017]


The integrator complex has been recently identified as a key regulator of RNA Polymerase II-mediated transcription, with many functions including the processing of small nuclear RNAs, the pause-release and elongation of polymerase during the transcription of protein coding genes, and the biogenesis of enhancer derived transcripts. Moreover, some of its components also play a role in genome maintenance. Thus, it is reasonable to hypothesize that their functional impairment or altered expression can contribute to malignancies. Indeed, several studies have described the mutations or transcriptional alteration of some Integrator genes in different cancers. Here, to draw a comprehensive pan-cancer picture of the genomic and transcriptomic alterations for the members of the complex, we reanalyzed public data from The Cancer Genome Atlas. Somatic mutations affecting Integrator subunit genes and their transcriptional profiles have been investigated in about 11,000 patients and 31 tumor types. A general heterogeneity in the mutation frequencies was observed, mostly depending on tumor type. Despite the fact that we could not establish them as cancer drivers, INTS7 and INTS8 genes were highly mutated in specific cancers. A transcriptome analysis of paired (normal and tumor) samples revealed that the transcription of INTS7, INTS8, and INTS13 is significantly altered in several cancers. Experimental validation performed on primary tumors confirmed these findings. View Full-Text
Keywords: integrator complex; somatic mutations; transcriptome profiling; human cancers; TCGA data analysis integrator complex; somatic mutations; transcriptome profiling; human cancers; TCGA data analysis

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Federico, A.; Rienzo, M.; Abbondanza, C.; Costa, V.; Ciccodicola, A.; Casamassimi, A. Pan-Cancer Mutational and Transcriptional Analysis of the Integrator Complex. Int. J. Mol. Sci. 2017, 18, 936.

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