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Inactivating mutations of CASPASE-7 gene in human cancers
Young Hwa Soung1, Jong Woo Lee, Hong Sug Kim
1College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, Korea.
Abstract:
Caspase-7 is a caspase involved in the execution phase of apoptosis. To explore the possibility that the genetic alterations of CASPASE-7 might be involved in the development of human cancers, we analysed the entire coding region and all splice sites of human CASPASE-7 gene for the detection of somatic mutations in a series of human solid cancers, including carcinomas from stomach, colon, head/neck, esophagus, urinary bladder and lung. Overall, we detected CASPASE-7 mutations in two of 98 colon carcinomas (2.0%), one of 50 esophageal carcinomas (2.0%) and one of 33 head/neck carcinomas (3.0%). We expressed the tumor-derived caspase-7 mutants in 293 T cells and found that the apoptosis was reduced compared to the wild-type caspase-7. This is the first report on the CASPASE-7 gene mutations in human malignancies, and our data suggest that the inactivating mutations of the CASPASE-7 gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some human solid cancers.
Insights
Genetic mutations in the CASPASE-7 gene were found in several human solid cancers. These CASPASE-7 gene mutations appear to reduce apoptosis, potentially contributing to cancer development.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Caspase-7 is a key enzyme in the programmed cell death (apoptosis) pathway.
- Dysregulation of apoptosis is a hallmark of cancer development.
- The role of CASP7 gene mutations in human cancers remains largely unexplored.
Purpose of the Study:
- To investigate the presence and functional impact of somatic mutations in the CASP7 gene in various human solid cancers.
- To determine if CASP7 alterations contribute to cancer pathogenesis.
Main Methods:
- Somatic mutation analysis of the entire coding region and splice sites of the human CASP7 gene.
- Analysis was performed on carcinomas from stomach, colon, head/neck, esophagus, urinary bladder, and lung.
- Functional assessment of tumor-derived CASP7 mutants by expression in 293 T cells to evaluate apoptotic activity.
Main Results:
- CASP7 mutations were identified in 2.0% of colon carcinomas (2/98) and esophageal carcinomas (1/50), and 3.0% of head/neck carcinomas (1/33).
- Tumor-derived CASP7 mutants exhibited reduced apoptotic activity compared to wild-type CASP7 when expressed in 293 T cells.
- This study represents the first report of CASP7 gene mutations in human malignancies.
Conclusions:
- Inactivating mutations in the CASP7 gene can lead to a loss of its apoptotic function.
- These CASP7 gene alterations may contribute to the development and progression of certain human solid cancers.
- Further research into CASP7's role in tumorigenesis is warranted.