NDLI: Whole-Exome Sequencing Identifies a Novel Germline Variant in PTK7 Gene in Familial Colorectal Cancer

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Whole-Exome Sequencing Identifies a Novel Germline Variant in PTK7 Gene in Familial Colorectal Cancer

Content Provider	MDPI
Author	Magdalena, Kuświk Wojciech, Kluźniak Asta, Försti Miao, Beiping Skopelitou, Diamanto Srivastava, Aayushi Giangiobbe, Sara Dymerska, Dagmara Paramasivam, Nagarajan Kumar, Abhishek Paszkowska-Szczur, Katarzyna Schlesner, Matthias Lubinski, Jan Hemminki, Kari Bandapalli, Obul Reddy
Copyright Year	2022
Description	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 of PTK7 and supported its role in genetic predisposition of familial CRC.
Starting Page	1295
e-ISSN	14220067
DOI	10.3390/ijms23031295
Journal	International Journal of Molecular Sciences
Issue Number	3
Volume Number	23
Language	English
Publisher	MDPI
Publisher Date	2022-01-24
Access Restriction	Open
Subject Keyword	International Journal of Molecular Sciences Oncology Colorectal Cancer Ptk7 Germline Variant Akt Signaling Pathway Familial Cancers Familial Cancer Variant Prioritization Pipeline
Content Type	Text
Resource Type	Article

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