Figure 6 from The Germline and Somatic Origins of...

Figure 6 from The Germline and Somatic Origins of Prostate Cancer Heterogeneity

Abstract

dQTLs bias somatic mutational landscape. A, Schematic of dQTL detection. The PRS used was by Schumacher and colleagues (<a href="#bib16" target="_blank">16</a>). Linear local dQTLs were assessed within ±500 kbp around a driver. Spatial local dQTLs were evaluated using regions defined by RNA Pol-II ChIA-PET profiling in LNCaP, DU145, VCaP, and RWPE-1 cell lines and RAD21 ChIA-PET in LNCaP and DU145 cells. Enhancer regions were defined using H3K27ac HiChIP profiling in LNCaP cells. All discovered dQTLs were tested for replication in six replication cohorts. B, Summary of 26 dQTLs involving 25 unique variants. Dot size and color indicate the magnitude and direction of ORs between the SNP and somatic driver. Background shading indicates P values. Covariate on left indicates type of somatic mutation; the top covariate indicates the analysis strategy for the discovery cohort . C, Comparison of ORs in the discovery vs. replication cohort for tag dQTLs. Horizontal and vertical dotted lines represent OR = 1, and the diagonal line represents y = x. Halo around points indicates replication of direction, diamond around points indicates Q < 0.1 in the replication cohort, and dot color indicates the somatic driver. D and E, Contingency tables for rs11203152 association with clonal loss of TMPRSS2 in (D) discovery and (E) replication cohorts. F and G, Contingency tables of rs848048 associated with SNVs in FOXA1 3′ UTR in (F) discovery and (G) replication cohorts.

Authors

Yamaguchi TN; Houlahan KE; Zhu H; Kurganovs N; Livingstone J; Fox NS; Yuan J; Sietsma Penington J; Jung C-H; Schwarz T

Publication Date

May 2, 2025

DOI

10.1158/2159-8290.28918315

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Katie Houlahan

Assistant Professor, Faculty of Health Sciences

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