Whole-Exome Sequencing Identifies a Novel Germline Variant in PTK7 Gene in Familial Colorectal Cancer
| Autor: | Miao Beiping, Skopelitou Diamanto, Srivastava AAyushi, Giangiobbe Sara, Dymerska Dagmara, Paramasivam Nagarajan, Kumar Abhishek, Kuswik Magdalena, Kluzniak Wojciech, Paszkowska-Szczur Katarzyna, Schlesner Matthias, Lubinski Jan, Hemminki Kari, Försti Asta, Bandapalli Obul Reddy |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
QH301-705.5
Organic Chemistry familial cancer variant prioritization pipeline colorectal cancer General Medicine PTK7 Catalysis digestive system diseases germline variant Computer Science Applications Inorganic Chemistry Chemistry AKT signaling pathway familial cancers ddc:610 Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences, Vol 23, Iss 1295, p 1295 (2022) International Journal of Molecular Sciences; Volume 23; Issue 3; Pages: 1295 |
| Popis: | Colorectal cancer (CRC) is the third most frequently diagnosed malignancy worldwide. Only 5% of all CRC cases are due to germline mutations in known predisposition genes, and the remaining genetic burden still has to be discovered. In this study, we performed whole-exome sequencing on six members of a Polish family diagnosed with CRC and identified a novel germline variant in the protein tyrosine kinase 7 (inactive) gene (PTK7, ENST00000230419, V354M). Targeted screening of the variant in 1705 familial CRC cases and 1674 healthy elderly individuals identified the variant in an additional familial CRC case. Introduction of this variant in HT-29 cells resulted in increased cell proliferation, migration, and invasion; it also caused down-regulation of CREB, p21 and p53 mRNA and protein levels, and increased AKT phosphorylation. These changes indicated inhibition of apoptosis pathways and activation of AKT signaling. Our study confirmed the oncogenic function ofPTK7and supported its role in genetic predisposition of familial CRC. |
| Databáze: | OpenAIRE |
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