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Purpose: To improve germline testing adoption for Veterans Affairs patients with metastatic prostate cancer (mPrCA), new delivery models were introduced to complement genetic consultation (traditional model), including mainstreaming where oncologists perform pre/posttest activities and a hybrid model where oncologists perform informed consent and then refer to genetics. We assessed germline testing adoption by delivery model.
Methods: We conducted a nationwide cohort study of mPrCA patients ascertained from May 3, 2021, to November 2, 2022, with follow-up through May 3, 2023. We assessed associations between patient and facility characteristics and having or completing germline test orders using Cox proportional hazards models.
Results: We identified 18,623 mPrCA patients. The average age was 73.9 years (SD, 8.3; range 35-102) with 59.6% non-Hispanic White and 28.9% non-Hispanic Black patients. The cumulative incidence of germline test orders was 13.7% over 2 years. Non-Hispanic Black patients were more likely than non-Hispanic White patients to have germline test orders (hazard ratio [HR], 1.28; 95% CI, 1.15-1.41) but less likely to complete their orders (HR, 0.81; 95% CI 0.72-0.91). Compared with non-Hispanic White patients, non-Hispanic Black patients were more likely to complete orders under the traditional model (HR, 1.40; 95% CI, 111-1.76), less likely under the hybrid model (HR, 0.62; 95% CI, 0.50-0.77) with no difference under the mainstream model.
Conclusion: Mainstreaming germline testing for mPrCA patients improved adoption without introducing disparities between non-Hispanic Black and White patients.
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http://dx.doi.org/10.1016/j.gim.2025.101383 | DOI Listing |
Genet Med
September 2025
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, Fulham Road, London, UK. Electronic address:
Purpose: Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a rare cancer susceptibility syndrome exclusively attributable to pathogenic variants in FH (HGNC:3700). This paper quantitatively weights the phenotypic context (PP4/PS4) of such very rare variants in FH.
Methods: We collated clinical diagnostic testing data on germline FH variants from 387 individuals with HLRCC and 1,780 individuals with renal cancer, and compared the frequency of 'very rare' variants in each phenotypic cohort against 562,295 population controls.
Eur J Obstet Gynecol Reprod Biol
August 2025
Reproductive Medicine Center, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen 518000 Guangdong, China; Shenzhen Clinical Research Center for Obstetrics & Gynecology and Reproductive System Diseases, Shenzhen 518000 Guangdong, China. Electronic address: szfyart
Objective: This study investigates the association between alobar holoprosencephaly (HPE) and de novo germline microdeletions in the Xq25 region. To develop a Preimplantation Genetic Testing for Monogenic Disorders (PGT-M) based workflow enabling high-resolution preimplantation detection of sub-Mb microdeletions, overcoming the >1 Mb resolution limit of conventional whole genome amplification(WGA) copy number variation(CNV) sequencing to identify causative Xq25 variants and prevent pathogenic microdeletion transmission.
Methods: This study presents a clinical case involving a couple with an adverse obstetric history accompanied by two occurrences of HPE.
Biologics
August 2025
Department of Internal Medicine, Section of Hematology and Medical Oncology, King Hussein Cancer Center, Amman, 11941, Jordan.
Purpose: Pancreatic cancer is one of the most lethal malignancies, with a five-year survival rate rarely exceeding 10%. Due to its asymptomatic onset, it is frequently diagnosed at an advanced and often inoperable stage. This review assesses current strategies for early detection, including genomic testing, advanced imaging technologies, and biomarker-based platforms, with a focus on their clinical utility and integration into surveillance protocols.
View Article and Find Full Text PDFCancer Epidemiol Biomarkers Prev
September 2025
Emory University, Atlanta, GA, United States.
Background: Half of ovarian high-grade serous carcinomas (HGSC) have homologous recombination deficiency (HRD). However, HRD is not well-characterized in Black individuals who experience worse survival after a diagnosis of HGSC. The objective of this study was to characterize ovarian HGSC HRD and examine its association with survival by self-reported race.
View Article and Find Full Text PDFHaematologica
September 2025
Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada; Department of Medicine, Queen's University, Kingston, ON.
Clonal hematopoiesis (CH) involves the expansion of hematopoietic stem cells with ageacquired mutations linked to myeloid malignancy. Advances in next-generation and single-cell sequencing, along with computational modeling, have expanded our ability to detect both common and rare CH drivers, including single-nucleotide variants and mosaic chromosomal alterations, with increasing sensitivity. While sequencing methods differ in accuracy, cost, and ability to detect low-frequency variants, they have deepened our understanding of CH biology.
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