Journal Article

DKFZ-2022-01054

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Whole exome sequencing identifies novel germline variants of SLC15A4 gene as potentially cancer predisposing in familial colorectal cancer.

Skopelitou, D. (First author)DKFZ* ; Srivastava, A.DKFZ* ; Miao, B.DKFZ* ; Kumar, A.DKFZ* ; Dymerska, D. ; Paramasivam, N. ; Schlesner, M.DKFZ* ; Lubinski, J. ; Hemminki, K.DKFZ* ; Försti, A.DKFZ* ; Reddy Bandapalli, O. (Last author)DKFZ*

2022
Springer New York, NY

This record in other databases:

Please use a persistent id in citations: doi:10.1007/s00438-022-01896-0

Abstract: About 15% of colorectal cancer (CRC) patients have first-degree relatives affected by the same malignancy. However, for most families the cause of familial aggregation of CRC is unknown. To identify novel high-to-moderate-penetrance germline variants underlying CRC susceptibility, we performed whole exome sequencing (WES) on four CRC cases and two unaffected members of a Polish family without any mutation in known CRC predisposition genes. After WES, we used our in-house developed Familial Cancer Variant Prioritization Pipeline and identified two novel variants in the solute carrier family 15 member 4 (SLC15A4) gene. The heterozygous missense variant, p. Y444C, was predicted to affect the phylogenetically conserved PTR2/POT domain and to have a deleterious effect on the function of the encoded peptide/histidine transporter. The other variant was located in the upstream region of the same gene (GRCh37.p13, 12_129308531_C_T; 43 bp upstream of transcription start site, ENST00000266771.5) and it was annotated to affect the promoter region of SLC15A4 as well as binding sites of 17 different transcription factors. Our findings of two distinct variants in the same gene may indicate a synergistic up-regulation of SLC15A4 as the underlying genetic cause and implicate this gene for the first time in genetic inheritance of familial CRC.

Keyword(s): Familial colorectal cancer ; Germline variant ; SLC15A4 ; Whole exome sequencing

Note: #EA:C050#LA:C050# / 2022 Jul;297(4):965-979

---

Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. Core Facility Omics IT (W610)
3. Molekular-Genetische Epidemiologie (C050)

Research Program(s):

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

Appears in the scientific report 2022

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---