DAB2IP with tumor-inhibiting activities exhibits frameshift mutations in gastrointestinal cancers
| Autor: | Hyun Ji Son, Yun Sol Jo, Nam Jin Yoo, Min Sung Kim, Sug Hyung Lee |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Tumor suppressor gene DNA Mutational Analysis Adenocarcinoma Biology medicine.disease_cause DNA sequencing Pathology and Forensic Medicine Frameshift mutation 03 medical and health sciences 0302 clinical medicine medicine Humans Coding region Genes Tumor Suppressor Frameshift Mutation neoplasms Gene Gastrointestinal Neoplasms Mutation Microsatellite instability Cell Biology medicine.disease digestive system diseases 030104 developmental biology ras GTPase-Activating Proteins 030220 oncology & carcinogenesis Cancer research Microsatellite Instability Carcinogenesis |
| Zdroj: | Pathology - Research and Practice. 214:2075-2080 |
| ISSN: | 0344-0338 |
| Popis: | A scaffold protein DAB2 and its interaction partner DAB2IP have putative tumor suppressor gene (TSG) functions. Previous studies identified that both DAB2 and DAB2IP genes were inactivated by promoter hypermethylation in human cancers, but their mutational alterations in cancers remain largely unknown. The aim of our study was to find whether DAB2 and DAB2IP were mutated in gastric (GCs) and colorectal cancers (CRCs) by DNA sequencing. Both DAB2 and DAB2IP have mononucleotide repeats in their coding sequence that could be mutation targets in high microsatellite instability (MSI-H) cancers. We analyzed GC and CRC tissues and found that 8 of 34 GCs (23.5%) and 15 of 79 CRCs (20.0%) with MSI-H harbored DAB2IP frameshift mutations. DAB2 frameshift mutations were found in 2 of 79 CRCs (2.5%) with MSI-H. These mutations were not detected in microsatellite stable (MSS) cancers. We also found intratumoral heterogeneity (ITH) of DAB2IP frameshift mutations in 7 of 16 CRCs (43.8%). Loss of DAB2IP protein expression was found in approximately 20% of GCs and CRCs irrespective of MSI and DAB2IP frameshift mutation status. Our study shows that the TSG DAB2IP harbored frameshift mutations and ITH as well as expression loss. Together these tumor alterations might play a role in tumorigenesis of GC and CRC with MSI-H by down-regulating the tumor-inhibiting activities of DAB2IP. |
| Databáze: | OpenAIRE |
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