SMARCA4 Pathogenic Variants Linked to Ovarian Cancer in New Study

Strategic Insights -

Research from a team at the August Pi i Sunyer Biomedical Research Institute has identified a link between SMARCA4 pathogenic variants and ovarian cancer. The study, published in Gynecologic Oncology, analyzed individuals with a SMARCA4 germline pathogenic/likely pathogenic variant (gPV) to inform guidance on surveillance and prevention. The study found that among individuals with a SMARCA4 gPV, 53.5% had a history of cancer, with 17.9% of these cases being small cell carcinoma of the ovary hypercalcemic type (SCCOHT).

Key Takeaways:

  • The study found that 137 individuals had a SMARCA4 gPV, with 127 included in the analysis after applying exclusion criteria.
  • The majority of individuals with a SMARCA4 gPV were female (74.8%), and 53.5% (n = 68) had a history of cancer.
  • Of the females with a cancer history, SCCOHT (17.9%) and ovarian cancer not otherwise specified (7.4%) were reported.
  • SCCOHT accounted for 29.8% of cancer diagnoses among females aged 50 years, with all SCCOHT cases among individuals with SMARCA4 gPVs diagnosed by age 40.
  • The study concluded that the data support the inclusion of SMARCA4 in genetic testing for hereditary early-onset ovarian cancer.
  • The study highlights the need for prospective penetrance studies to improve counseling and management for patients and their families.

Statistics:

  • 137 individuals had a SMARCA4 gPV.
  • 127 individuals were included in the analysis after applying exclusion criteria.
  • 74.8% of individuals with a SMARCA4 gPV were female.
  • 53.5% (n = 68) of individuals with a SMARCA4 gPV had a history of cancer.
  • 17.9% of females with a cancer history had SCCOHT.
  • 7.4% of females with a cancer history had ovarian cancer not otherwise specified.
  • SCCOHT accounted for 29.8% of cancer diagnoses among females aged 50 years.

Sources:

  • SMARCA4 pathogenic variants: Gynecological cancer histories from a laboratory tested cohort. Gynecologic Oncology, 2025;202:125-130.
  • Gynecologic Oncology, Academic Press Inc Elsevier Science, 525 B St, Ste 1900, San Diego, CA 92101-4495, USA, www.elsevier.com, www.journals.elsevier.com/gynecologic-oncology/
  • NewsRx. Recent Findings in Ovarian Cancer Described by Researchers from August Pi i Sunyer Biomedical Research Institute. OBGYN & Reproduction Week. October 27, 2025; p 619.