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PR/SET Domain Family and Cancer: Novel Insights from The Cancer Genome Atlas

The PR/SET domain gene family (PRDM) encodes 19 different transcription factors that share a subtype of the SET domain [Su(var)3-9, enhancer-of-zeste and trithorax] known as the PRDF1-RIZ (PR) homology domain. This domain, with its potential methyltransferase activity, is followed by a variable numb...

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Autores principales: Sorrentino, Anna, Federico, Antonio, Rienzo, Monica, Gazzerro, Patrizia, Bifulco, Maurizio, Ciccodicola, Alfredo, Casamassimi, Amelia, Abbondanza, Ciro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214140/
https://www.ncbi.nlm.nih.gov/pubmed/30347759
http://dx.doi.org/10.3390/ijms19103250
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author Sorrentino, Anna
Federico, Antonio
Rienzo, Monica
Gazzerro, Patrizia
Bifulco, Maurizio
Ciccodicola, Alfredo
Casamassimi, Amelia
Abbondanza, Ciro
author_facet Sorrentino, Anna
Federico, Antonio
Rienzo, Monica
Gazzerro, Patrizia
Bifulco, Maurizio
Ciccodicola, Alfredo
Casamassimi, Amelia
Abbondanza, Ciro
author_sort Sorrentino, Anna
collection PubMed
description The PR/SET domain gene family (PRDM) encodes 19 different transcription factors that share a subtype of the SET domain [Su(var)3-9, enhancer-of-zeste and trithorax] known as the PRDF1-RIZ (PR) homology domain. This domain, with its potential methyltransferase activity, is followed by a variable number of zinc-finger motifs, which likely mediate protein–protein, protein–RNA, or protein–DNA interactions. Intriguingly, almost all PRDM family members express different isoforms, which likely play opposite roles in oncogenesis. Remarkably, several studies have described alterations in most of the family members in malignancies. Here, to obtain a pan-cancer overview of the genomic and transcriptomic alterations of PRDM genes, we reanalyzed the Exome- and RNA-Seq public datasets available at The Cancer Genome Atlas portal. Overall, PRDM2, PRDM3/MECOM, PRDM9, PRDM16 and ZFPM2/FOG2 were the most mutated genes with pan-cancer frequencies of protein-affecting mutations higher than 1%. Moreover, we observed heterogeneity in the mutation frequencies of these genes across tumors, with cancer types also reaching a value of about 20% of mutated samples for a specific PRDM gene. Of note, ZFPM1/FOG1 mutations occurred in 50% of adrenocortical carcinoma patients and were localized in a hotspot region. These findings, together with OncodriveCLUST results, suggest it could be putatively considered a cancer driver gene in this malignancy. Finally, transcriptome analysis from RNA-Seq data of paired samples revealed that transcription of PRDMs was significantly altered in several tumors. Specifically, PRDM12 and PRDM13 were largely overexpressed in many cancers whereas PRDM16 and ZFPM2/FOG2 were often downregulated. Some of these findings were also confirmed by real-time-PCR on primary tumors.
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spelling pubmed-62141402018-11-14 PR/SET Domain Family and Cancer: Novel Insights from The Cancer Genome Atlas Sorrentino, Anna Federico, Antonio Rienzo, Monica Gazzerro, Patrizia Bifulco, Maurizio Ciccodicola, Alfredo Casamassimi, Amelia Abbondanza, Ciro Int J Mol Sci Article The PR/SET domain gene family (PRDM) encodes 19 different transcription factors that share a subtype of the SET domain [Su(var)3-9, enhancer-of-zeste and trithorax] known as the PRDF1-RIZ (PR) homology domain. This domain, with its potential methyltransferase activity, is followed by a variable number of zinc-finger motifs, which likely mediate protein–protein, protein–RNA, or protein–DNA interactions. Intriguingly, almost all PRDM family members express different isoforms, which likely play opposite roles in oncogenesis. Remarkably, several studies have described alterations in most of the family members in malignancies. Here, to obtain a pan-cancer overview of the genomic and transcriptomic alterations of PRDM genes, we reanalyzed the Exome- and RNA-Seq public datasets available at The Cancer Genome Atlas portal. Overall, PRDM2, PRDM3/MECOM, PRDM9, PRDM16 and ZFPM2/FOG2 were the most mutated genes with pan-cancer frequencies of protein-affecting mutations higher than 1%. Moreover, we observed heterogeneity in the mutation frequencies of these genes across tumors, with cancer types also reaching a value of about 20% of mutated samples for a specific PRDM gene. Of note, ZFPM1/FOG1 mutations occurred in 50% of adrenocortical carcinoma patients and were localized in a hotspot region. These findings, together with OncodriveCLUST results, suggest it could be putatively considered a cancer driver gene in this malignancy. Finally, transcriptome analysis from RNA-Seq data of paired samples revealed that transcription of PRDMs was significantly altered in several tumors. Specifically, PRDM12 and PRDM13 were largely overexpressed in many cancers whereas PRDM16 and ZFPM2/FOG2 were often downregulated. Some of these findings were also confirmed by real-time-PCR on primary tumors. MDPI 2018-10-19 /pmc/articles/PMC6214140/ /pubmed/30347759 http://dx.doi.org/10.3390/ijms19103250 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sorrentino, Anna
Federico, Antonio
Rienzo, Monica
Gazzerro, Patrizia
Bifulco, Maurizio
Ciccodicola, Alfredo
Casamassimi, Amelia
Abbondanza, Ciro
PR/SET Domain Family and Cancer: Novel Insights from The Cancer Genome Atlas
title PR/SET Domain Family and Cancer: Novel Insights from The Cancer Genome Atlas
title_full PR/SET Domain Family and Cancer: Novel Insights from The Cancer Genome Atlas
title_fullStr PR/SET Domain Family and Cancer: Novel Insights from The Cancer Genome Atlas
title_full_unstemmed PR/SET Domain Family and Cancer: Novel Insights from The Cancer Genome Atlas
title_short PR/SET Domain Family and Cancer: Novel Insights from The Cancer Genome Atlas
title_sort pr/set domain family and cancer: novel insights from the cancer genome atlas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214140/
https://www.ncbi.nlm.nih.gov/pubmed/30347759
http://dx.doi.org/10.3390/ijms19103250
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