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| Verfasst von: | Skopelitou, Diamanto [VerfasserIn]  |
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| | Miao, Beiping [VerfasserIn] |
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| | Srivastava, Aayushi [VerfasserIn] |
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| | Kumar, Abhishek [VerfasserIn] |
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| | Kuświk, Magdalena [VerfasserIn] |
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| | Dymerska, Dagmara [VerfasserIn] |
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| | Paramasivam, Nagarajan [VerfasserIn] |
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| | Schlesner, Matthias [VerfasserIn] |
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| | Lubiński, Jan [VerfasserIn] |
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| | Hemminki, Kari [VerfasserIn] |
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| | Försti, Asta [VerfasserIn] |
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| | Bandapalli, Obul Reddy [VerfasserIn] |
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| Titel: | A novel low-risk germline variant in the SH2 domain of the SRC gene affects multiple pathways in familial colorectal cancer |
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| Verf.angabe: | Diamanto Skopelitou, Beiping Miao, Aayushi Srivastava, Abhishek Kumar, Magdalena Kuświk, Dagmara Dymerska, Nagarajan Paramasivam, Matthias Schlesner, Jan Lubiński, Kari Hemminki, Asta Försti, Obul Reddy Bandapalli |
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| E-Jahr: | 2021 |
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| Jahr: | 1 April 2021 |
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| Umfang: | 15 S. |
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| Fussnoten: | Gesehen am 26.05.2021 |
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| Titel Quelle: | Enthalten in: Journal of Personalized Medicine |
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| Ort Quelle: | Basel : MDPI, 2011 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 11(2021), 4, Artikel-ID 262, Seite 1-15 |
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| ISSN Quelle: | 2075-4426 |
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| Abstract: | Colorectal cancer (CRC) shows one of the largest proportions of familial cases among different malignancies, but only 5-10% of all CRC cases are linked to mutations in established predisposition genes. Thus, familial CRC constitutes a promising target for the identification of novel, high- to moderate-penetrance germline variants underlying cancer susceptibility by next generation sequencing. In this study, we performed whole genome sequencing on three members of a family with CRC aggregation. Subsequent integrative in silico analysis using our in-house developed variant prioritization pipeline resulted in the identification of a novel germline missense variant in the SRC gene (V177M), a proto-oncogene highly upregulated in CRC. Functional validation experiments in HT-29 cells showed that introduction of SRCV177M resulted in increased cell proliferation and enhanced protein expression of phospho-SRC (Y419), a potential marker for SRC activity. Upregulation of paxillin, β-Catenin, and STAT3 mRNA levels, increased levels of phospho-ERK, CREB, and CCND1 proteins and downregulation of the tumor suppressor p53 further proposed the activation of several pathways due to the SRCV177M variant. The findings of our pedigree-based study contribute to the exploration of the genetic background of familial CRC and bring insights into the molecular basis of upregulated SRC activity and downstream pathways in colorectal carcinogenesis. |
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| DOI: | doi:10.3390/jpm11040262 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.3390/jpm11040262 |
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| | Volltext: https://www.mdpi.com/2075-4426/11/4/262 |
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| | DOI: https://doi.org/10.3390/jpm11040262 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | familial colorectal cancer |
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| | germline variant |
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| | SRC |
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| | whole genome sequencing |
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| K10plus-PPN: | 1758739428 |
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| Verknüpfungen: | → Zeitschrift |
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¬A¬ novel low-risk germline variant in the SH2 domain of the SRC gene affects multiple pathways in familial colorectal cancer / Skopelitou, Diamanto [VerfasserIn]; 1 April 2021 (Online-Ressource)
