STK11 – familial Ovarian Cancer

In a multi-gene next-generation sequencing panel study of hereditary ovarian carcinoma, STK11 was included among DNA damage response genes associated with familial risk, but no specific germline STK11 variants were annotated (PMID:32895312). The overall hereditary predisposition in the cohort was estimated at ~23%, with BRCA1/2 accounting for the majority of cases and STK11 contributing marginally to non-BRCA familial ovarian cancer.

Functional characterization of STK11 has focused on its role as a tumor suppressor in Peutz–Jeghers syndrome. Pathogenic truncating and missense variants across the kinase domain lead to loss of LKB1 kinase activity, impaired AMPK pathway activation, disrupted cell polarity, and defective p53-mediated transcriptional activation. However, no direct functional assays have validated STK11 loss in ovarian epithelial models or clarified its mechanistic contribution to ovarian tumorigenesis.

Currently, the association between STK11 and familial ovarian cancer is supported solely by panel-based sequencing data with no variant- or segregation-specific evidence. Additional case series with STK11-positive probands and targeted functional studies in ovarian tissue are required to establish clinical utility.

Key take-home: STK11 is a plausible predisposition gene in non-BRCA familial ovarian cancer, but evidence remains limited and insufficient for routine risk assessment.

References

• International journal of gynecological cancer : official journal of the International Gynecological Cancer Society • 2020 • Ovarian cancer predisposition beyond BRCA1 and BRCA2 genes PMID:32895312

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