Aberrant MUC1-TRIM46-KRTCAP2 Chimeric RNAs in High-Grade Serous Ovarian Carcinoma
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,...
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MDPI AG
2015-10-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/7/4/0878 |
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| author | Kalpana Kannan Gona Karimi Kordestani Anika Galagoda Cristian Coarfa Laising Yen |
| author_facet | Kalpana Kannan Gona Karimi Kordestani Anika Galagoda Cristian Coarfa Laising Yen |
| author_sort | Kalpana Kannan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T19:13:32Z |
| format | Article |
| id | doaj.art-d562541337e34624a53dfadc74274e1d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T19:13:32Z |
| publishDate | 2015-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d562541337e34624a53dfadc74274e1d2023-08-02T05:44:27ZengMDPI AGCancers2072-66942015-10-01742083209310.3390/cancers7040878cancers7040878Aberrant MUC1-TRIM46-KRTCAP2 Chimeric RNAs in High-Grade Serous Ovarian CarcinomaKalpana Kannan0Gona Karimi Kordestani1Anika Galagoda2Cristian Coarfa3Laising Yen4Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USADepartment of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USAHigh-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.http://www.mdpi.com/2072-6694/7/4/0878chimeric RNAhigh-grade serous ovarian cancerMUC1TCGARNA-seq |
| spellingShingle | Kalpana Kannan Gona Karimi Kordestani Anika Galagoda Cristian Coarfa Laising Yen Aberrant MUC1-TRIM46-KRTCAP2 Chimeric RNAs in High-Grade Serous Ovarian Carcinoma Cancers chimeric RNA high-grade serous ovarian cancer MUC1 TCGA RNA-seq |
| title | Aberrant MUC1-TRIM46-KRTCAP2 Chimeric RNAs in High-Grade Serous Ovarian Carcinoma |
| title_full | Aberrant MUC1-TRIM46-KRTCAP2 Chimeric RNAs in High-Grade Serous Ovarian Carcinoma |
| title_fullStr | Aberrant MUC1-TRIM46-KRTCAP2 Chimeric RNAs in High-Grade Serous Ovarian Carcinoma |
| title_full_unstemmed | Aberrant MUC1-TRIM46-KRTCAP2 Chimeric RNAs in High-Grade Serous Ovarian Carcinoma |
| title_short | Aberrant MUC1-TRIM46-KRTCAP2 Chimeric RNAs in High-Grade Serous Ovarian Carcinoma |
| title_sort | aberrant muc1 trim46 krtcap2 chimeric rnas in high grade serous ovarian carcinoma |
| topic | chimeric RNA high-grade serous ovarian cancer MUC1 TCGA RNA-seq |
| url | http://www.mdpi.com/2072-6694/7/4/0878 |
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