TY  - JOUR
AU  - Niazi, Yasmeen
AU  - Paramasivam, Nagarajan
AU  - Blocka, Joanna
AU  - Kumar, Abhishek
AU  - Huhn, Stefanie
AU  - Schlesner, Matthias
AU  - Weinhold, Niels
AU  - Sijmons, Rolf
AU  - De Jong, Mirjam
AU  - Durie, Brian
AU  - Goldschmidt, Hartmut
AU  - Hemminki, Kari
AU  - Försti, Asta
TI  - Investigation of Rare Non-Coding Variants in Familial Multiple Myeloma.
JO  - Cells
VL  - 12
IS  - 1
SN  - 2073-4409
CY  - Basel
PB  - MDPI
M1  - DKFZ-2023-00057
SP  - 96
PY  - 2023
N1  - #EA:B062#LA:B062#
AB  - Multiple myeloma (MM) is a plasma cell malignancy whereby a single clone of plasma cells over-propagates in the bone marrow, resulting in the increased production of monoclonal immunoglobulin. While the complex genetic architecture of MM is well characterized, much less is known about germline variants predisposing to MM. Genome-wide sequencing approaches in MM families have started to identify rare high-penetrance coding risk alleles. In addition, genome-wide association studies have discovered several common low-penetrance risk alleles, which are mainly located in the non-coding genome. Here, we further explored the genetic basis in familial MM within the non-coding genome in whole-genome sequencing data. We prioritized and characterized 150 upstream, 5' untranslated region (UTR) and 3' UTR variants from 14 MM families, including 20 top-scoring variants. These variants confirmed previously implicated biological pathways in MM development. Most importantly, protein network and pathway enrichment analyses also identified 10 genes involved in mitogen-activated protein kinase (MAPK) signaling pathways, which have previously been established as important MM pathways.
KW  - MAPK pathway (Other)
KW  - familial multiple myeloma (Other)
KW  - non-coding genome (Other)
KW  - whole-genome sequencing (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36611892
DO  - DOI:10.3390/cells12010096
UR  - https://inrepo02.dkfz.de/record/186688
ER  -