Assessment of candidate high-grade serous ovarian carcinoma predisposition genes through integrated germline and tumour sequencing.

High-grade serous ovarian carcinoma (HGSOC) has a significant hereditary component, only half of which is explained. Previously, we performed germline exome sequencing on BRCA1 and BRCA2-negative HGSOC patients, revealing three proposed and 43 novel candidate genes enriched with rare loss-of-function variants. For validation, we undertook case-control analyses using genomic data from disease-free controls.

Reduced Breast and Ovarian Cancer Through Targeted Genetic Testing: Estimates Using the NEEMO Microsimulation Model.

The effectiveness and cost-effectiveness of genetic testing for hereditary breast and ovarian cancer largely rely on the identification and clinical management of individuals with a pathogenic variant prior to developing cancer. Simulation modelling is commonly utilised to evaluate genetic testing strategies due to its ability to synthesise collections of data and extrapolate over long time periods and large populations. Existing genetic testing simulation models use simplifying assumptions for predictive genetic testing and risk management uptake, which could impact the reliability of their estimates.

Distribution of prostatic markers in glands of the female urethra and anterior vaginal wall-a rapid autopsy study.

Background: There are varying reports of immunohistochemically detected prostatic marker protein distribution in glands associated with the female urethra that may be related to tissue integrity at the time of fixation.

Aim: In this study we used tissue derived from rapid autopsies of female patients to determine the distribution of glandular structures expressing prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) along the female urethra and in surrounding tissues, including the anterior vaginal wall (AVW).

Methods: Tissue blocks from 7 donors that contained the entire urethra and adjacent AVW were analyzed.

Research autopsy programmes in oncology: shared experience from 14 centres across the world.

While there is a great clinical need to understand the biology of metastatic cancer in order to treat it more effectively, research is hampered by limited sample availability. Research autopsy programmes can crucially advance the field through synchronous, extensive, and high-volume sample collection. However, it remains an underused strategy in translational research.

ENIGMA CHEK2gether Project: A Comprehensive Study Identifies Functionally Impaired CHEK2 Germline Missense Variants Associated with Increased Breast Cancer Risk.

Purpose: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT).