Journal Article

DKFZ-2022-00442

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Whole-Exome Sequencing Identifies a Novel Germline Variant in PTK7 Gene in Familial Colorectal Cancer.

Miao, B. (First author)DKFZ* ; Skopelitou, D.DKFZ* ; Srivastava, A.DKFZ* ; Giangiobbe, S.DKFZ* ; Dymerska, D. ; Paramasivam, N. ; Kumar, A.DKFZ* ; Kuświk, M. ; Kluźniak, W. ; Paszkowska-Szczur, K. ; Schlesner, M.DKFZ* ; Lubinski, J. ; Hemminki, K.DKFZ* ; Försti, A.DKFZ* ; Bandapalli, O. R. (Last author)DKFZ*

2022
Molecular Diversity Preservation International Basel

This record in other databases:

Please use a persistent id in citations: doi:10.3390/ijms23031295

Abstract: 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.

Keyword(s): Aged (MeSH) ; Cell Adhesion Molecules: genetics (MeSH) ; Cell Adhesion Molecules: metabolism (MeSH) ; Cell Movement: genetics (MeSH) ; Cell Proliferation: genetics (MeSH) ; Colorectal Neoplasms: genetics (MeSH) ; Colorectal Neoplasms: pathology (MeSH) ; Cyclic AMP Response Element-Binding Protein: genetics (MeSH) ; Cyclin-Dependent Kinase Inhibitor p21: genetics (MeSH) ; Family (MeSH) ; Female (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Germ-Line Mutation: genetics (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Neoplasm Invasiveness: genetics (MeSH) ; Oncogenes (MeSH) ; Pedigree (MeSH) ; Proto-Oncogene Proteins c-akt: genetics (MeSH) ; Receptor Protein-Tyrosine Kinases: genetics (MeSH) ; Receptor Protein-Tyrosine Kinases: metabolism (MeSH) ; Tumor Suppressor Protein p53: genetics (MeSH) ; Whole Exome Sequencing: methods (MeSH) ; AKT signaling pathway ; PTK7 ; colorectal cancer ; familial cancer variant prioritization pipeline ; familial cancers ; germline variant ; CDKN1A protein, human ; CREB1 protein, human ; Cell Adhesion Molecules ; Cyclic AMP Response Element-Binding Protein ; Cyclin-Dependent Kinase Inhibitor p21 ; Tumor Suppressor Protein p53 ; PTK7 protein, human ; Receptor Protein-Tyrosine Kinases ; Proto-Oncogene Proteins c-akt

Note: #EA:B062#LA:B062#

---

Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)
3. Molekular-Genetische Epidemiologie (C050)
4. W610 Omics IT and Data Management (W610)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2022

---

Database coverage:
; ; ; Article Processing Charges ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---