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Dynamic control of RNA-DNA hybrid formation orchestrates DNA2 activation at stalled forks by RNAPII and DDX39A.
Mol Cell
December 2024
Department of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310058 Hangzhou, China; Department of Cell Biology, Zhejiang University School of Medicine, 310058 Hangzhou, China. Electronic address:
Stalled replication forks, susceptible to nucleolytic threats, necessitate protective mechanisms involving pivotal factors such as the tumor suppressors BRCA1 and BRCA2. Here, we demonstrate that, upon replication stress, RNA polymerase II (RNAPII) is recruited to stalled forks, actively promoting the transient formation of RNA-DNA hybrids. These hybrids act as safeguards, preventing premature engagement by the DNA2 nuclease and uncontrolled DNA2-mediated degradation of nascent DNA.
View Article and Find Full Text PDFHigh-grade serous carcinoma occurring after risk-reducing salpingo-oophorectomy in BRCA1/2 germline pathogenic variant carriers.
J Natl Cancer Inst
November 2024
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Article Synopsis
- Risk-reducing salpingo-oophorectomy (RRSO) significantly lowers the risk of high-grade serous carcinoma (HGSC) in women carrying BRCA1/2 genetic variants, but some still develop HGSC after the procedure.
- A study involving 2,519 women found that the 20-year cumulative incidence of HGSC was low (1.5% for BRCA1 and 0.2% for BRCA2 carriers), with particular risk factors identified, such as older age at RRSO and incomplete embedding of RRSO specimens.
- Implementing strict guidelines for timely RRSO and ensuring complete specimen embedding could further minimize the risk of developing HGSC in these patients
Oncologic outcomes of incidental serous tubal intraepithelial carcinoma and associated high-grade serous carcinoma in high-risk patients undergoing risk-reducing surgery.
Int J Gynecol Cancer
January 2025
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Objective: We sought to describe the oncologic outcomes of isolated serous tubal intraepithelial carcinomas compared to an intraepithelial carcinoma found concurrently with microscopic high-grade serous carcinoma among patients with hereditary predisposition to ovarian cancer who underwent risk-reducing surgery.
Methods: We conducted a retrospective analysis of 32 high-risk patients with or pathogenic variants who were diagnosed with either isolated serous tubal intraepithelial carcinoma or concurrent serous tubal intraepithelial carcinoma and microscopic high-grade serous carcinoma following risk-reducing surgery between January 2006 and December 2023. Our population included patients who underwent surgery at our institution as well as those who had surgery elsewhere, but sought second opinions, follow-up care, or treatment at our institution.
Deletions Rate-Limit Breast and Ovarian Cancer Initiation.
bioRxiv
October 2024
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Optimizing prevention and early detection of cancer requires understanding the number, types and timing of driver mutations. To quantify this, we exploited the elevated cancer incidence and mutation rates in germline and carriers. Using novel statistical models, we identify genomic deletions as the likely rate-limiting mutational processes, with 1-3 deletions required to initiate breast and ovarian tumors.
View Article and Find Full Text PDFDecision-making process for risk-reducing salpingo-oophorectomy among Korean women with hereditary breast cancer: A grounded theory study.
Eur J Oncol Nurs
December 2024
Mo-Im Kim Nursing Research Institute, College of Nursing, Yonsei University, 03722, Seoul, South Korea. Electronic address:
Purpose: To explore the decision-making process regarding Risk-Reducing Salpingo-Oophorectomy (RRSO) among women with hereditary breast cancer in Korea, with a focus on complex interpersonal interactions and sociocultural influences.
Method: This qualitative, grounded theory study conducted semi-structured and in-depth interviews with 17 women with hereditary breast cancer between March and December 2021. Theoretical sampling and constant comparison were utilized for data analysis.
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