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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Gene expression profiling and real-time PCR analyses identify novel potential cancer-testis antigens in multiple
Maud Condomines1, Dirk Hose, Thierry Rème
1Centre Hospitalier Universitaire Montpellier, Institute of Research in Biotherapy, Montpellier, France.
Abstract:
Cancer-testis (CT) Ags are attractive targets for immunotherapeutic strategies since they are aberrantly expressed in malignant cells and not, or in limited number, in somatic tissues, except germ cells. To identify novel CT genes in multiple myeloma, we used Affymetrix HG-U133 gene expression profiles of 5 testis, 64 primary multiple myeloma cells (MMC), and 24 normal tissue samples. A 5-filter method was developed to keep known CT genes while deleting non-CT genes. Starting from 44,928 probe sets, including probe sets for 18 previously described CT genes, we have obtained 82 genes expressed in MMC and testis and not detected in more than 6 normal tissue samples. This list includes 14 of the 18 known CT genes and 68 novel putative CT genes. Real-time RT-PCR was performed for 34 genes in 12 normal tissue samples, 5 MMC samples, and one sample of five pooled testes. It has validated the CT status of 23 of 34 genes (67%). We found one novel "testis-restricted" gene (TEX14, expression in testis and tumor only), eight "tissue-restricted" (mRNA detected in one or two nongametogenic tissues), and seven "differentially expressed" (mRNA detected in three to six nongametogenic tissues) CT genes. Further studies are warranted to determine the immunogenicity of these novel CT Ag candidates.
Insights
Researchers identified 68 novel cancer-testis (CT) genes in multiple myeloma, offering new targets for immunotherapy. These CT antigens are expressed in tumors but not in most normal tissues, making them promising for cancer treatment strategies.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Cancer-testis (CT) antigens are aberrantly expressed in malignancies and are potential targets for immunotherapy.
- Identifying novel CT antigens is crucial for developing effective cancer treatments.
Purpose of the Study:
- To identify novel CT genes in multiple myeloma (MM).
- To evaluate the expression profiles of these genes in MM and normal tissues.
Main Methods:
- Utilized Affymetrix HG-U133 gene expression profiles from testis, primary multiple myeloma cells (MMC), and normal tissues.
- Developed a 5-filter method to identify known and novel CT genes.
- Validated CT gene status using real-time RT-PCR.
Main Results:
- Identified 82 genes expressed in MMC and testis, not detected in most normal tissues.
- This list includes 14 known CT genes and 68 novel putative CT genes.
- Validated the CT status of 23 out of 34 tested genes (67%), including testis-restricted and tissue-restricted CT genes.
Conclusions:
- Discovered 68 novel CT gene candidates for multiple myeloma.
- These novel CT antigens represent promising targets for future cancer immunotherapeutic strategies.
- Further research is needed to assess the immunogenicity of these novel CT antigen candidates.
