Highly recurrent mutations of SGK1, DUSP2 and JUNB in nodular lymphocyte predominant Hodgkin lymphoma

Hartmann, Sven; Schuhmacher, Bianca; Rausch, Tobias; Fuller, Laphalle; Döring, Claudia; Weniger, Marc A.; Lollies, Anna; Weiser, Christian; Thurner, Lorenz; Rengstl, Benjamin; Brunnberg, Uta; Vornanen, Martine; Pfreundschuh, Michael; Beneš, Vladimı́r; Küppers, Ralf; Newrzela, Sebastian; Ml, Hansmann

doi:10.1038/leu.2015.328

Cited by 82 publications

(76 citation statements)

References 54 publications

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“…Similar to AKT isoforms, SGK1 does not appear to be frequently mutated in human tumors, although a recent study has found frequent SGK1 mutations (approximately 50% of samples) in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) (Hartmann et al, 2016). The functional significance of these alterations remains anyway to be defined.…”

Section: Sgk1 and Cancermentioning

confidence: 99%

Sgk1

Cristofano

2017

Current Topics in Developmental Biology

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Activation of the PI3K pathway is central to a variety of physiological and pathological processes. In these contexts, AKT is classically considered the de facto mediator of PI3K-dependent signaling. However, in recent years, accumulating data point to the existence of additional effectors of PI3K activity, parallel to and independent of AKT, that play critical and unique roles in mediating different developmental, homeostatic, and pathological processes. In this review, I summarize and discuss our current understanding of the function of the serine/threonine kinase SGK1 as a downstream effector of PI3K, and try to separate targets and pathways validated as uniquely SGK1-dependent from those shared with AKT.

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Section: Sgk1 and Cancermentioning

confidence: 99%

Sgk1

Cristofano

2017

Current Topics in Developmental Biology

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“…Genome-wide, this identified 649 somatic eQTL (FDR ≤ 5%; Supplementary Table 4) associated with 567 unique regions. Among these, 11 somatic eQTL were explained by mutational burdens in exons or introns, including genes with known roles in the pathogenesis of specific cancers such as CDK12 in ovarian cancer 29,30 , PI4KA in hepatocellular carcinoma 31 , IRF4 in leukemia 32 , AICDA in skin melanoma 33 , C11orf73 in clear cell renal cancer 34 and BCL2 and SGK1 in lymphoma 35 , Extended Data Figure 12a-g). The majority of eGenes (68.4%) involved associations with flanking non-coding intervals (272 intergenic, 172 intronic regions, Figure 2d), and were due to mutations observed in multiple cancers (Extended Data Figure 13a, Supplementary Table 4).…”

Section: Somatic Cis Eqtl Mapping Reveals Widespread Associations Witmentioning

confidence: 99%

Genomic basis for RNA alterations revealed by whole-genome analyses of 27 cancer types

Calabrese¹,

Davidson

Fonseca³

et al. 2017

Preprint

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We present the most comprehensive catalogue of cancer-associated gene alterations through characterization of tumor transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes project. Using matched whole-genome sequencing data, we attributed RNA alterations to germline and somatic DNA alterations, revealing likely genetic mechanisms. We identified 444 associations of gene expression with somatic non-coding single-nucleotide variants. We found 1,872 splicing alterations associated with somatic mutation in intronic regions, including novel exonization events associated with Alu elements. Somatic copy number alterations were the major driver of total gene and allele-specific expression (ASE) variation. Additionally, 82% of gene fusions had structural variant support, including 75 of a novel class called “bridged” fusions, in which a third genomic location bridged two different genes. Globally, we observe transcriptomic alteration signatures that differ between cancer types and have associations with DNA mutational signatures. Given this unique dataset of RNA alterations, we also identified 1,012 genes significantly altered through both DNA and RNA mechanisms. Our study represents an extensive catalog of RNA alterations and reveals new insights into the heterogeneous molecular mechanisms of cancer gene alterations.

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“…Genome-wide, this identified 649 somatic eQTL (FDR ≤ 5%; Table S6 ) in 567 genomic regions. Among these, 11 somatic eQTL were explained by the mutational burden in exons or introns, including genes with known roles in the pathogenesis of specific cancers such as CDK12 in ovarian cancer (Bajrami et al 2013;Ekumi et al 2015) , PI4KA in hepatocellular carcinoma (Ilboudo et al 2014) , IRF4 in leukemia (Havelange et al 2011) , AICDA in skin melanoma (Nonaka et al 2016) , C11orf73 in clear cell renal cancer (Bhalla et al 2017) and BCL2 and SGK1 in lymphoma (Weinhold et al 2014 ;Hartmann et al 2016 , Fig. S12 A-G ).…”

Section: Somatic Eqtl Mapping Reveals Widespread Associations With Nomentioning

confidence: 99%

Assessing the Gene Regulatory Landscape in 1,188 Human Tumors

Calabrese

Lehmann

Urban

et al. 2017

Preprint

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Cancer is characterised by somatic genetic variation, but the effect of the majority of non-coding somatic variants and the interface with the germline genome are still unknown. We analysed the whole genome and RNA-Seq data from 1,188 human cancer patients as provided by the Pan-cancer Analysis of Whole Genomes (PCAWG) project to map cis expression quantitative trait loci of somatic and germline variation and to uncover the causes of allele-specific expression patterns in human cancers. The availability of the first large-scale dataset with both whole genome and gene expression data enabled us to uncover the effects of the non-coding variation on cancer. In addition to confirming known regulatory effects, we identified novel associations between somatic variation and expression dysregulation, in particular in distal regulatory elements. Finally, we uncovered links between somatic mutational signatures and gene expression changes, including TERT and LMO2 , and we explained the inherited risk factors in APOBEC-related mutational processes. This work represents the first large-scale assessment of the effects of both germline and somatic genetic variation on gene expression in cancer and creates a valuable resource cataloguing these effects.

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Highly recurrent mutations of SGK1, DUSP2 and JUNB in nodular lymphocyte predominant Hodgkin lymphoma

Cited by 82 publications

References 54 publications

Sgk1

Sgk1

Genomic basis for RNA alterations revealed by whole-genome analyses of 27 cancer types

Assessing the Gene Regulatory Landscape in 1,188 Human Tumors

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