bims-ovdlit 2024-06-23 papers

Issue of 2024–06–23
five papers selected by
Lara Paracchini, Humanitas Research

Fam Cancer. 2024 Jun 21.

Risk-reducing salpingectomy with delayed oophorectomy to prevent ovarian cancer in women with an increased inherited risk: insights into an alternative strategy.

T A Gootzen, M P Steenbeek, Mhd van Bommel, J IntHout, C M Kets, Rpmg Hermens, J A de Hullu.

Epithelial ovarian cancer (EOC) is the most lethal type of gynaecological cancer, due to lack of effective screening possibilities and because the disease tends to metastasize before onset of symptoms. Women with an increased inherited risk for EOC are advised to undergo a risk-reducing salpingo-oophorectomy (RRSO), which decreases their EOC risk by 96% when performed within guideline ages. However, it also induces premature menopause, which has harmful consequences. There is compelling evidence that the majority of EOCs originate in the fallopian tube. Therefore, a risk-reducing salpingectomy with delayed oophorectomy (RRS with DO) has gained interest as an alternative strategy. Previous studies have shown that this alternative strategy has a positive effect on menopause-related quality of life and sexual health when compared to the standard RRSO. It is hypothesized that the alternative strategy is non-inferior to the standard RRSO with respect to oncological safety (EOC incidence). Three prospective studies are currently including patients to compare the safety and/or quality of life of the two distinct strategies. In this article we discuss the background, opportunities, and challenges of the current and alternative strategy.

Keywords: BRCA1; BRCA2; Carcinoma; Gynaecologic Surgical procedures; Ovarian Cancer; Prevention

DOI: https://doi.org/10.1007/s10689-024-00412-0

Nat Genet. 2024 Jun 18.

Analysis of 10,478 cancer genomes identifies candidate driver genes and opportunities for precision oncology.

Ben Kinnersley, Amit Sud, Andrew Everall, Alex J Cornish, Daniel Chubb, Richard Culliford, Andreas J Gruber, Adrian Lärkeryd, Costas Mitsopoulos, David Wedge, Richard Houlston.

Tumor genomic profiling is increasingly seen as a prerequisite to guide the treatment of patients with cancer. To explore the value of whole-genome sequencing (WGS) in broadening the scope of cancers potentially amenable to a precision therapy, we analysed whole-genome sequencing data on 10,478 patients spanning 35 cancer types recruited to the UK 100,000 Genomes Project. We identified 330 candidate driver genes, including 74 that are new to any cancer. We estimate that approximately 55% of patients studied harbor at least one clinically relevant mutation, predicting either sensitivity or resistance to certain treatments or clinical trial eligibility. By performing computational chemogenomic analysis of cancer mutations we identify additional targets for compounds that represent attractive candidates for future clinical trials. This study represents one of the most comprehensive efforts thus far to identify cancer driver genes in the real world setting and assess their impact on informing precision oncology.

DOI: https://doi.org/10.1038/s41588-024-01785-9

Cell Rep Methods. 2024 Jun 17. pii: S2667-2375(24)00149-8. [Epub ahead of print]4(6): 100793

Systematic biases in reference-based plasma cell-free DNA fragmentomic profiling.

Xiaoyi Liu, Mengqi Yang, Dingxue Hu, Yunyun An, Wanqiu Wang, Huizhen Lin, Yuqi Pan, Jia Ju, Kun Sun.

Plasma cell-free DNA (cfDNA) fragmentation patterns are emerging directions in cancer liquid biopsy with high translational significance. Conventionally, the cfDNA sequencing reads are aligned to a reference genome to extract their fragmentomic features. In this study, through cfDNA fragmentomics profiling using different reference genomes on the same datasets in parallel, we report systematic biases in such conventional reference-based approaches. The biases in cfDNA fragmentomic features vary among races in a sample-dependent manner and therefore might adversely affect the performances of cancer diagnosis assays across multiple clinical centers. In addition, to circumvent the analytical biases, we develop Freefly, a reference-free approach for cfDNA fragmentomics profiling. Freefly runs ∼60-fold faster than the conventional reference-based approach while generating highly consistent results. Moreover, cfDNA fragmentomic features reported by Freefly can be directly used for cancer diagnosis. Hence, Freefly possesses translational merit toward the rapid and unbiased measurement of cfDNA fragmentomics.

Keywords: CP: Systems biology; cancer diagnosis; end motif; liquid biopsy; size profile

DOI: https://doi.org/10.1016/j.crmeth.2024.100793