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Uterine lavage identifies cancer mutations and increased somatic mutation burden in individuals with ovarian cancer. | LitMetric

AI Article Synopsis

  • * A study involving 34 patients showed that ultra-deep sequencing successfully identified tumor mutations in 33% of early-stage non-serous ovarian cancers and 79% of serous cancers, indicating the method's potential for early detection.
  • * Lavage samples revealed a high number of background mutations and distinct patterns of driver mutations linked to ovarian cancer, suggesting that mutation burden could be an important factor in assessing ovarian cancer risk.

Article Abstract

Current screening methods for ovarian cancer (OC) have failed to demonstrate a significant reduction in mortality. Uterine lavage combined with ultra-deep sequencing for the detection of disseminated OC cells has emerged as a promising tool, but this approach has not been tested for early-stage disease or non-serous histologies. In addition, lavages carry multiple background mutations, the significance of which is poorly understood. Uterine lavage was collected preoperatively in 34 patients undergoing surgery for suspected ovarian malignancy including 14 patients with benign disease and 20 patients with OC (6 non-serous and 14 high grade serous-like (serous)). Ultra-deep duplex sequencing (~3000x) with a panel of common OC genes identified the tumor mutation in 33% of non-serous (all early stage) and in 79% of serous cancers (including four early stage). In addition, all lavages carried multiple somatic mutations (average of 25 mutations per lavage), more than half of which corresponded to common cancer driver mutations. Driver mutations in and presented as larger clones than non-driver mutations and with similar frequency in lavages from patients with and without OC, indicating prevalent somatic evolution in all patients. Driver mutations, however, presented as significantly larger clones and with higher frequency in lavages from individuals with OC, suggesting that -specific clonal expansions are linked to ovarian cancer development. Our results demonstrate that lavages capture cancer cells, even from early-stage cancers, as well as other clonal expansions and support further exploration of mutation burden as a potential OC risk factor.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9615025PMC
http://dx.doi.org/10.1158/2767-9764.crc-22-0314DOI Listing

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