AI Article Synopsis

  • Ovarian cancer is highly lethal and often diagnosed at late stages, necessitating a study of genetic variants in a cohort of 351 Belgian patients to identify treatment options.
  • The analysis revealed that BRCA1 and BRCA2 variants were present in a small percentage of patients, while a broader multi-gene panel identified numerous additional variants, particularly in genes like TP53 and PIK3CA.
  • The study concludes that while few genetic variants currently influence treatment decisions, many others could lead to personalized treatment strategies, especially for rarer ovarian cancer types.

Article Abstract

Ovarian cancer is the most lethal gynecologic malignancy, mainly due to late-stage diagnosis, frequent recurrences, and eventually therapy resistance. To identify potentially actionable genetic variants, sequencing data of 351 Belgian ovarian cancer patients were retrospectively captured from electronic health records. The cohort included 286 (81%) patients with high-grade serous ovarian cancer, 17 (5%) with low-grade serous ovarian cancer, and 48 (14%) with other histotypes. Firstly, an overview of the prevalence and spectrum of the BRCA1/2 variants highlighted germline variants in 4% (11/250) and somatic variants in 11% (37/348) of patients. Secondly, application of a multi-gene panel in 168 tumors revealed a total of 214 variants in 28 genes beyond BRCA1/2 with a median of 1 (IQR, 1-2) genetic variant per patient. The ten most often altered genes were (in descending order): TP53, BRCA1, PIK3CA, BRCA2, KRAS, ERBB2 (HER2), TERT promotor, RB1, PIK3R1 and PTEN. Of note, the genetic landscape vastly differed between the studied histotypes. Finally, using ESCAT the clinical evidence of utility for every genetic variant was scored. Only BRCA1/2 pathogenic variants were classified as tier-I. Nearly all patients (151/168; 90%) had an ESCAT tier-II variant, most frequently in TP53 (74%), PIK3CA (9%) and KRAS (7%). In conclusion, our findings imply that although only a small proportion of genetic variants currently have direct impact on ovarian cancer treatment decisions, other variants could help to identify novel (personalized) treatment options to address the poor prognosis of ovarian cancer, particularly in rare histotypes.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10959961PMC
http://dx.doi.org/10.1038/s41698-024-00565-2DOI Listing

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