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| Home > Publications database > A Novel Low-Risk Germline Variant in the SH2 Domain of the SRC Gene Affects Multiple Pathways in Familial Colorectal Cancer. > print |
| Home > Publications database > A Novel Low-Risk Germline Variant in the SH2 Domain of the SRC Gene Affects Multiple Pathways in Familial Colorectal Cancer. > print |
| 001 | 168696 | ||
| 005 | 20240229133613.0 | ||
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| 100 | 1 | _ | |a Skopelitou, Diamanto |0 P:(DE-He78)cea283034a4f6c64994f85d4444e7494 |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a A Novel Low-Risk Germline Variant in the SH2 Domain of the SRC Gene Affects Multiple Pathways in Familial Colorectal Cancer. |
| 260 | _ | _ | |a Basel |c 2021 |b MDPI |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1620224023_15353 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a #EA:C050#LA:C050# |
| 520 | _ | _ | |a 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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| 650 | _ | 7 | |a SRC |2 Other |
| 650 | _ | 7 | |a familial colorectal cancer |2 Other |
| 650 | _ | 7 | |a germline variant |2 Other |
| 650 | _ | 7 | |a whole genome sequencing |2 Other |
| 700 | 1 | _ | |a Miao, Beiping |0 P:(DE-He78)b5b786a7a28d851956ba90aa9451887a |b 1 |u dkfz |
| 700 | 1 | _ | |a Srivastava, Aayushi |0 P:(DE-He78)43b43c5f20ed70299251a446ad8ec973 |b 2 |
| 700 | 1 | _ | |a Kumar, Abhishek |b 3 |
| 700 | 1 | _ | |a Kuświk, Magdalena |0 0000-0001-9070-747X |b 4 |
| 700 | 1 | _ | |a Dymerska, Dagmara |0 0000-0001-8097-8014 |b 5 |
| 700 | 1 | _ | |a Paramasivam, Nagarajan |b 6 |
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| 700 | 1 | _ | |a Lubiński, Jan |b 8 |
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| 700 | 1 | _ | |a Bandapalli, Obul Reddy |0 P:(DE-He78)b11ccde1801d45d32a6a60f7b396d7dc |b 11 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.3390/jpm11040262 |g Vol. 11, no. 4, p. 262 - |0 PERI:(DE-600)2662248-8 |n 4 |p 262 |t Journal of Personalized Medicine |v 11 |y 2021 |x 2075-4426 |
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