Transcriptome Analyses Identify Deregulated <i>MYC</i> in Early Onset Colorectal Cancer

Despite a global decrease in colorectal cancer (CRC) incidence, the prevalence of early-onset colorectal cancer (EOCRC), or those occurring in individuals before the age of 50, has steadily increased over the past several decades. When compared to later onset colorectal cancer (LOCRC) in individuals...

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Main Authors: Olivia M. Marx, Marc M. Mankarious, Melanie A. Eshelman, Wei Ding, Walter A. Koltun, Gregory S. Yochum
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/12/9/1223
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author Olivia M. Marx
Marc M. Mankarious
Melanie A. Eshelman
Wei Ding
Walter A. Koltun
Gregory S. Yochum
author_facet Olivia M. Marx
Marc M. Mankarious
Melanie A. Eshelman
Wei Ding
Walter A. Koltun
Gregory S. Yochum
author_sort Olivia M. Marx
collection DOAJ
description Despite a global decrease in colorectal cancer (CRC) incidence, the prevalence of early-onset colorectal cancer (EOCRC), or those occurring in individuals before the age of 50, has steadily increased over the past several decades. When compared to later onset colorectal cancer (LOCRC) in individuals over 50, our understanding of the genetic and molecular underpinnings of EOCRCs is limited. Here, we conducted transcriptomic analyses of patient-matched normal colonic segments and tumors to identify gene expression programs involved in carcinogenesis. Amongst differentially expressed genes, we found increased expression of the <i>c-MYC</i> proto-oncogene (<i>MYC</i>) and its downstream targets in tumor samples. We identified tumors with high and low differential <i>MYC</i> expression and found patients with high-<i>MYC</i> tumors were older and overweight or obese. We also detected elevated expression of the <i>PVT1</i> long-non-coding RNA (lncRNA) in most tumors and found gains in copy number for both <i>MYC</i> and <i>PVT1</i> gene loci in 35% of tumors evaluated. Our transcriptome analyses indicate that EOCRC can be sub-classified into groups based on differential <i>MYC</i> expression and suggest that deregulated <i>MYC</i> contributes to CRCs that develop in younger patients.
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spelling doaj.art-3b72e533a9a5400990d33be42b34f3f72023-11-23T15:14:56ZengMDPI AGBiomolecules2218-273X2022-09-01129122310.3390/biom12091223Transcriptome Analyses Identify Deregulated <i>MYC</i> in Early Onset Colorectal CancerOlivia M. Marx0Marc M. Mankarious1Melanie A. Eshelman2Wei Ding3Walter A. Koltun4Gregory S. Yochum5Department of Biochemistry & Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USADepartment of Surgery, Division of Colon & Rectal Surgery, Pennsylvania State University College of Medicine, Hershey, PA 17033, USADepartment of Pediatrics, Division of Hematology & Oncology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USADepartment of Surgery, Division of Colon & Rectal Surgery, Pennsylvania State University College of Medicine, Hershey, PA 17033, USADepartment of Surgery, Division of Colon & Rectal Surgery, Pennsylvania State University College of Medicine, Hershey, PA 17033, USADepartment of Biochemistry & Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USADespite a global decrease in colorectal cancer (CRC) incidence, the prevalence of early-onset colorectal cancer (EOCRC), or those occurring in individuals before the age of 50, has steadily increased over the past several decades. When compared to later onset colorectal cancer (LOCRC) in individuals over 50, our understanding of the genetic and molecular underpinnings of EOCRCs is limited. Here, we conducted transcriptomic analyses of patient-matched normal colonic segments and tumors to identify gene expression programs involved in carcinogenesis. Amongst differentially expressed genes, we found increased expression of the <i>c-MYC</i> proto-oncogene (<i>MYC</i>) and its downstream targets in tumor samples. We identified tumors with high and low differential <i>MYC</i> expression and found patients with high-<i>MYC</i> tumors were older and overweight or obese. We also detected elevated expression of the <i>PVT1</i> long-non-coding RNA (lncRNA) in most tumors and found gains in copy number for both <i>MYC</i> and <i>PVT1</i> gene loci in 35% of tumors evaluated. Our transcriptome analyses indicate that EOCRC can be sub-classified into groups based on differential <i>MYC</i> expression and suggest that deregulated <i>MYC</i> contributes to CRCs that develop in younger patients.https://www.mdpi.com/2218-273X/12/9/1223early-onset colorectal cancerRNA-sequencingtranscriptomeMYCPVT1
spellingShingle Olivia M. Marx
Marc M. Mankarious
Melanie A. Eshelman
Wei Ding
Walter A. Koltun
Gregory S. Yochum
Transcriptome Analyses Identify Deregulated <i>MYC</i> in Early Onset Colorectal Cancer
Biomolecules
early-onset colorectal cancer
RNA-sequencing
transcriptome
MYC
PVT1
title Transcriptome Analyses Identify Deregulated <i>MYC</i> in Early Onset Colorectal Cancer
title_full Transcriptome Analyses Identify Deregulated <i>MYC</i> in Early Onset Colorectal Cancer
title_fullStr Transcriptome Analyses Identify Deregulated <i>MYC</i> in Early Onset Colorectal Cancer
title_full_unstemmed Transcriptome Analyses Identify Deregulated <i>MYC</i> in Early Onset Colorectal Cancer
title_short Transcriptome Analyses Identify Deregulated <i>MYC</i> in Early Onset Colorectal Cancer
title_sort transcriptome analyses identify deregulated i myc i in early onset colorectal cancer
topic early-onset colorectal cancer
RNA-sequencing
transcriptome
MYC
PVT1
url https://www.mdpi.com/2218-273X/12/9/1223
work_keys_str_mv AT oliviammarx transcriptomeanalysesidentifyderegulatedimyciinearlyonsetcolorectalcancer
AT marcmmankarious transcriptomeanalysesidentifyderegulatedimyciinearlyonsetcolorectalcancer
AT melanieaeshelman transcriptomeanalysesidentifyderegulatedimyciinearlyonsetcolorectalcancer
AT weiding transcriptomeanalysesidentifyderegulatedimyciinearlyonsetcolorectalcancer
AT walterakoltun transcriptomeanalysesidentifyderegulatedimyciinearlyonsetcolorectalcancer
AT gregorysyochum transcriptomeanalysesidentifyderegulatedimyciinearlyonsetcolorectalcancer