Somatic Genomic and Transcriptomic Characterization of Primary Ovarian Serous Borderline Tumors and Low-Grade Serous Carcinomas

Stružinská, Ivana; Hájková, Nikola; Hojný, Jan; Krkavcová, Eva; Michálková, Romana; Bui, Quang Hiep; Matěj, Radoslav; Laco, Jan; Drozenová, Jana; Fabian, Pavel; Škapa, Petr; Špůrková, Zuzana; Cibula, David; Frühauf, Filip; Jirásek, Tomáš; Zima, Tomáš; Méhes, Gábor; Kendall Bártů, Michaela; Němejcová, Kristýna; Dundr, Pavel

doi:10.1016/j.jmoldx.2023.12.004

Cited by 4 publications

(1 citation statement)

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“…Considering polygenic inheritance from an alternative perspective, we observed significant variability in GPV burden among different OC types and super-controls. Higher GPV burden was identified in patients diagnosed with invasive epithelial OC and, remarkably, GPV burden tended to increase with increasing somatic genomic instability characteristic for each histological OC types 40 , 63 . Interestingly, Qing et al .…”

Section: Discussionmentioning

confidence: 89%

A comprehensive analysis of germline predisposition to early-onset ovarian cancer

Horackova,

Zemankova,

Nehasil

et al. 2024

Sci Rep

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The subset of ovarian cancer (OC) diagnosed ≤ 30yo represents a distinct subgroup exhibiting disparities from late-onset OC in many aspects, including indefinite germline cancer predisposition. We performed DNA/RNA-WES with HLA-typing, PRS assessment and survival analysis in 123 early-onset OC-patients compared to histology/stage-matched late-onset and unselected OC-patients, and population-matched controls. Only 6/123(4.9%) early-onset OC-patients carried a germline pathogenic variant (GPV) in high-penetrance OC-predisposition genes. Nevertheless, our comprehensive germline analysis of early-onset OC-patients revealed two divergent trajectories of potential germline susceptibility. Firstly, overrepresentation analysis highlighted a connection to breast cancer (BC) that was supported by the CHEK2 GPV enrichment in early-onset OC(p = 1.2 × 10–4), and the presumably BC-specific PRS313, which successfully stratified early-onset OC-patients from controls(p = 0.03). The second avenue pointed towards the impaired immune response, indicated by LY75-CD302 GPV(p = 8.3 × 10–4) and diminished HLA diversity compared with controls(p = 3 × 10–7). Furthermore, we found a significantly higher overall GPV burden in early-onset OC-patients compared to controls(p = 3.8 × 10–4). The genetic predisposition to early-onset OC appears to be a heterogeneous and complex process that goes beyond the traditional Mendelian monogenic understanding of hereditary cancer predisposition, with a significant role of the immune system. We speculate that rather a cumulative overall GPV burden than specific GPV may potentially increase OC risk, concomitantly with reduced HLA diversity.

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Section: Discussionmentioning

confidence: 89%