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Cancers 2015, 7(4), 2083-2093; doi:10.3390/cancers7040878

Aberrant MUC1-TRIM46-KRTCAP2 Chimeric RNAs in High-Grade Serous Ovarian Carcinoma

1
Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USA
2
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
3
Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
4
Center for Drug Discovery, Baylor College of Medicine, Houston, TX 77030, USA
Current address: Islamic Azad University Science and Research branch, Tehran 1477893855, Iran.
*
Author to whom correspondence should be addressed.
Academic Editor: Camile S. Farah
Received: 4 August 2015 / Revised: 28 September 2015 / Accepted: 8 October 2015 / Published: 19 October 2015
(This article belongs to the Special Issue Next Generation Sequencing Approaches in Cancer)
View Full-Text   |   Download PDF [825 KB, uploaded 19 October 2015]   |  

Abstract

High-grade serous ovarian cancer (HGSC) is among the most lethal forms of cancer in women. By analyzing the mRNA-seq reads from The Cancer Genome Atlas (TCGA), we uncovered a novel cancer-enriched chimeric RNA as the result of splicing between MUC1, a highly glycosylated transmembrane mucin, TRIM46, a tripartite motif containing protein, and KRTCAP2, a keratinocyte associated protein. Experimental analyses by RT-PCR (reverse transcription PCR) and Sanger sequencing using an in-house cohort of 59 HGSC patient tumors revealed a total of six MUC1-TRIM46-KRTCAP2 isoforms joined by different annotated splice sites between these genes. These chimeric isoforms are not detected in non-cancerous ovaries, yet are present in three out of every four HGSC patient tumors, a significant frequency given the exceedingly heterogeneous nature of this disease. Transfection of the cDNA of MUC1-TRIM46-KRTCAP2 isoforms in mammalian cells led to the translation of mutant MUC1 fusion proteins that are unglycosylated and cytoplasmically localized as opposed to the cell membrane, a feature resembling the tumor-associated MUC1. Because the parental MUC1 is overexpressed in 90% of HGSC tumors and has been proposed as a clinical biomarker and therapeutic target, the chimeric MUC1-TRIM46-KRTCAP2 isoforms identified in this report could represent significantly better MUC1 variants for the same clinical utilities. View Full-Text
Keywords: chimeric RNA; high-grade serous ovarian cancer; MUC1; TCGA; RNA-seq chimeric RNA; high-grade serous ovarian cancer; MUC1; TCGA; RNA-seq
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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MDPI and ACS Style

Kannan, K.; Kordestani, G.K.; Galagoda, A.; Coarfa, C.; Yen, L. Aberrant MUC1-TRIM46-KRTCAP2 Chimeric RNAs in High-Grade Serous Ovarian Carcinoma. Cancers 2015, 7, 2083-2093.

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