Oncotarget

Research Papers:

Genomic alterations in mucins across cancers

Ryan J. King, Fang Yu and Pankaj K. Singh _

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Oncotarget. 2017; 8:67152-67168. https://doi.org/10.18632/oncotarget.17934

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Abstract

Ryan J. King1, Fang Yu2 and Pankaj K. Singh1,3,4,5

1The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA

2Department of Biostatistics, University of Nebraska Medical Center, Omaha, Nebraska, USA

3Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA

4Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA

5Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, USA

Correspondence to:

Pankaj K. Singh email: pankaj.singh@unmc.edu

Keywords: mucins, MUC1, cancer genetics, genetic alterations, cancer genetic profiles

Received: March 06, 2017     Accepted: May 02, 2017     Published: May 17, 2017

ABSTRACT

The significance of mucins in cancers has led to the development of novel biomarkers and therapeutic agents against cancers. Despite significant advances in the understanding of mucins, systemic investigations into the role of mucins in cancer biology focusing particularly on the histological subtypes and stages, along with other variables, are yet to be carried out to discover potential novel functions and cancer-specific roles. Here, we investigated 11 mucin expressing cancers for DNA mutations, mRNA expression, copy number, methylation, and the impacts these genomic features may have on patient survival by utilizing The Cancer Genome Atlas dataset. We demonstrate that mucin DNA mutations have a significant rate, pattern, and impact on cancer patient survival depending on the tissue of origin. This includes a frequent T112P mutation in MUC1 that is seen in half of the pancreatic MUC1 mutations, as well as being present in other cancers. We also observed a very frequent MUC4 mutation at H4205, which correlated with survival outcomes in patients. Furthermore, we observed significant alterations in mucin mRNA expression in multiple tumor types. Our results demonstrate de novo expression of certain mucins in cancer tissues, including MUC21 in colorectal cancers. We observed a general decrease in promoter methylation for mucins, which correlated with decreased expression of many genes, such as MUC15 in kidney cancers. Lastly, several mucin gene loci demonstrated copy number increase in multiple histological subtypes. Thus, our study presents a comprehensive analysis of genomic alterations in mucins and their corresponding roles in cancer progression.


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