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Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
Mutational analysis of PTPRT phosphatase domains in common human cancers
Jong Woo Lee1, Eun Goo Jeong, Sung Hak Lee
1Department of Pathology, College of Medicine, Catholic University of Korea, Seoul, Korea.
Abstract:
A recent report revealed that the protein-tyrosine phosphatase, receptor-type, T (PTPRT) gene is somatically mutated in several types of human cancer, suggesting that the mutated PTPRT gene is a tumor suppressor gene in human cancers. However, because previously the mutational search has focused primarily on colon cancers, data on PTPRT mutations in other types of human cancer have largely been lacking. Here, we performed a mutational analysis of the PTPRT phosphatase domain by polymerase chain reaction-based single-strand conformation polymorphism (PCR-SSCP) assay in 345 cases of common human cancers, including colon carcinomas, hepatocellular carcinomas, acute leukemias, gastric carcinomas, breast carcinomas and non-small cell lung cancers. We detected PTPRT phosphatase domain mutations in 1 of 105 colon carcinomas (1%) and 1 of 48 gastric carcinomas (2%), but none in acute leukemias, hepatocellular carcinomas, breast carcinomas and non-small cell lung cancers. The PTPRT mutation detected in the colon carcinoma was a missense mutation and the mutation in the gastric carcinomas was a splice-site mutation. Contrary to the previous report on the frequent PTPTR phosphatase domain mutations in colon cancers, this study demonstrated that the somatic mutation of the PTPRT phosphatase domain rarely occurred in common human cancers. The data suggested that alterations of the PTPRT-mediated signaling pathway by PTPRT phosphatase domain mutation may not play a critical role in the development of common human cancers.
Insights
Somatic mutations in the protein-tyrosine phosphatase, receptor-type, T (PTPRT) gene are rare in common human cancers. This suggests PTPRT mutations may not be a critical factor in the development of most cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The protein-tyrosine phosphatase, receptor-type, T (PTPRT) gene has been implicated as a potential tumor suppressor due to somatic mutations in some cancers.
- Previous research on PTPRT mutations primarily focused on colon cancer, leaving data on other cancer types limited.
Purpose of the Study:
- To investigate the frequency and types of PTPRT phosphatase domain mutations across a broader spectrum of common human cancers.
- To evaluate the role of PTPRT mutations in the pathogenesis of various cancer types.
Main Methods:
- A mutational analysis of the PTPRT phosphatase domain was conducted using polymerase chain reaction-based single-strand conformation polymorphism (PCR-SSCP) assay.
- The study analyzed 345 cases of common human cancers, including colon, gastric, liver, leukemia, breast, and non-small cell lung cancers.
Main Results:
- PTPRT phosphatase domain mutations were detected in 1 out of 105 colon carcinomas (1%) and 1 out of 48 gastric carcinomas (2%).
- No PTPRT mutations were found in hepatocellular carcinomas, acute leukemias, breast carcinomas, or non-small cell lung cancers.
- The identified mutations included a missense mutation in colon cancer and a splice-site mutation in gastric cancer.
Conclusions:
- Somatic mutations in the PTPRT phosphatase domain are rare in the common human cancers examined.
- Alterations in the PTPRT-mediated signaling pathway due to PTPRT phosphatase domain mutations likely do not play a critical role in the development of most common human cancers.
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