Oncotarget

Research Papers:

Aberrant chimeric RNA GOLM1-MAK10 encoding a secreted fusion protein as a molecular signature for human esophageal squamous cell carcinoma

Hao Zhang _, Wan Lin, Kalpana Kannan, Liming Luo, Jing Li, Pei-Wen Chao, Yan Wang, Yu-Ping Chen, Jiang Gu and Laising Yen

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Oncotarget. 2013; 4:2135-2143. https://doi.org/10.18632/oncotarget.1465

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Abstract

Hao Zhang1,2,3, Wan Lin2, Kalpana Kannan4,5, Liming Luo4,5, Jing Li6, Pei-Wen Chao4,5, Yan Wang4,5, Yu-Ping Chen7, Jiang Gu6, Laising Yen4,5

1 Department of Integrative Oncology, Affiliated Cancer Hospital, Shantou University Medical College, Shantou, Guangdong, China.

2 Cancer Research Center, Shantou University Medical College, Shantou, Guangdong, China.

3 Tumor Tissue Bank, Affiliated Cancer Hospital, Shantou University Medical College, Shantou, Guangdong, China.

4 Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA.

5 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.

6 Department of Pathology, Shantou University Medical College, Shantou, Guangdong, China.

7 Department of Thoracic Surgery, Affiliated Cancer Hospital, Shantou University Medical College, Shantou, Guangdong, China.

Correspondence:

Hao Zhang, email:

Laising Yen, email:

Keywords: Transcriptome, transcription-induced chimeric RNAs, GOLM1-MAK10, secreted fusion protein, cancer biomarker, esophageal cancer.

Received: October 7, 2013 Accepted: October 30, 2013 Published: November 1, 2013

Abstract

It is increasingly recognized that chimeric RNAs may exert a novel layer of cellular complexity that contributes to oncogenesis and cancer progression, and could be utilized as molecular biomarkers and therapeutic targets. To date yet no fusion chimeric RNAs have been identified in esophageal cancer, the 6th most frequent cause of cancer death in the world. While analyzing the expression of 32 recurrent cancer chimeric RNAs in esophageal squamous cell carcinoma (ESCC) from patients and cancer cell lines, we identified GOLM1-MAK10, as a highly cancer-enriched chimeric RNA in ESCC. In situ hybridization revealed that the expression of the chimera is largely restricted to cancer cells in patient tumors, and nearly undetectable in non-neoplastic esophageal tissue from normal subjects. The aberrant chimera closely correlated with histologic differentiation and lymph node metastasis. Furthermore, we demonstrate that chimera GOLM1-MAK10 encodes a secreted fusion protein. Mechanistic studies reveal that GOLM1-MAK10 is likely derived from transcription read-through/splicing rather than being generated from a fusion gene. Collectively, these findings provide novel insights into the molecular mechanism involved in ESCC and provide a novel potential target for future therapies. The secreted fusion protein translated from GOLM1-MAK10 could also serve as a unique protein signature detectable by standard non-invasive assays. These observations are critical as there is no clinically useful molecular signature available for detecting this deadly disease or monitoring the treatment response.


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