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Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
Published on: July 22, 2020
Isolation of LEM domain-containing 1, a novel testis-specific gene expressed in colorectal cancers
Daisuke Yuki1, Yu-Min Lin, Yoshitaka Fujii
1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Abstract:
Through analysis of genome-wide expression profiles on a cDNA microarray consisting of 23,040 human genes, we have been attempting to isolate novel molecular targets for diagnosis, treatment and prevention of colorectal carcinoma (CRC). Among the genes that were frequently transactivated in colorectal tumors, we identified a novel gene termed LEMD1 (LEM domain-containing 1) whose expression was elevated in 17 of 18 CRCs compared with their corresponding non-cancerous mucosae. Northern blotting revealed that LEMD1 was expressed only in testis among the 16 normal adult tissues examined. Subsequent analysis identified six alternatively spliced forms of the transcript in normal testis, but only one of them (656 nucleotides) was expressed in CRCs. Since the LEMD1 protein appears to fall in the category of cancer-testis antigens (CTAs), it may represent a promising target antigen for immunotherapy of CRCs.
Insights
Researchers identified a novel gene, LEMD1, highly expressed in colorectal carcinoma (CRC) tumors but not normal tissues. This finding suggests LEMD1 as a potential target for CRC diagnosis and immunotherapy.
Area of Science:
- Genomics
- Molecular Biology
- Oncology
Background:
- Colorectal carcinoma (CRC) presents a significant health burden, necessitating novel diagnostic and therapeutic targets.
- Genome-wide expression profiling is a powerful tool for identifying genes implicated in cancer development.
Purpose of the Study:
- To identify novel molecular targets for the diagnosis, treatment, and prevention of colorectal carcinoma (CRC).
- To investigate the expression patterns of LEMD1 in CRC and normal tissues.
Main Methods:
- Genome-wide expression profiling using a cDNA microarray with 23,040 human genes.
- Northern blotting to analyze LEMD1 expression in various normal adult tissues and CRC samples.
- Analysis of alternative splicing variants of LEMD1 transcripts.
Main Results:
- A novel gene, LEM domain-containing 1 (LEMD1), was identified with significantly elevated expression in 17 out of 18 CRC samples compared to non-cancerous mucosa.
- LEMD1 expression was predominantly observed in the testis among 16 normal adult tissues examined.
- A specific alternatively spliced transcript of LEMD1 (656 nucleotides) was found to be expressed in CRCs.
Conclusions:
- LEMD1 is frequently transactivated in colorectal tumors and exhibits restricted expression in normal tissues, primarily the testis.
- The LEMD1 protein is classified as a cancer-testis antigen (CTA).
- LEMD1 represents a promising target antigen for the development of novel immunotherapies for colorectal carcinoma.
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