دورية أكاديمية
أعرض في EDS

Uterine lavage identifies cancer mutations and increased TP53 somatic mutation burden in individuals with ovarian cancer.

التفاصيل البيبلوغرافية
العنوان: Uterine lavage identifies cancer mutations and increased TP53 somatic mutation burden in individuals with ovarian cancer.
المؤلفون: Ghezelayagh TS; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, USA., Kohrn BF; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, USA., Fredrickson J; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, USA., Manhardt E; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA., Radke MR; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA., Katz R; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA., Gray HJ; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA., Urban RR; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA., Pennington KP; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA., Liao JB; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA., Doll KM; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA., Simons EJ; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA., Burzawa JK; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA., Goff BA; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA., Speiser P; Medical University of Vienna, Austria., Swisher EM; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA., Norquist BM; Department of Obstetrics and Gynecology, University of Washington, Seattle, USA., Risques RA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, USA.
المصدر: Cancer research communications [Cancer Res Commun] 2022 Oct; Vol. 2 (10), pp. 1282-1292. Date of Electronic Publication: 2022 Oct 27.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9918281580506676 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2767-9764 (Electronic) Linking ISSN: 27679764 NLM ISO Abbreviation: Cancer Res Commun
أسماء مطبوعة: Original Publication: [Philadelphia, Pennsylvania] : American Association for Cancer Research, [2021]-
مواضيع طبية MeSH: Therapeutic Irrigation* , Ovarian Neoplasms*/genetics, Humans ; Female ; Mutation/genetics ; Clonal Evolution ; Tumor Suppressor Protein p53/genetics
مستخلص: Current screening methods for ovarian cancer (OC) have failed to demonstrate a significant reduction in mortality. Uterine lavage combined with TP53 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 KRAS, PIK3CA, PTEN, PPP2R1A and ARID1A 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 TP53 mutations, however, presented as significantly larger clones and with higher frequency in lavages from individuals with OC, suggesting that TP53 -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 TP53 mutation burden as a potential OC risk factor.
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معلومات مُعتمدة: R01 CA259384 United States CA NCI NIH HHS; R21 CA240885 United States CA NCI NIH HHS; P30 CA015704 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Uterine lavage; clonal expansions; ovarian cancer; somatic evolution
المشرفين على المادة: 0 (TP53 protein, human)
0 (Tumor Suppressor Protein p53)
تواريخ الأحداث: Date Created: 20221031 Date Completed: 20230731 Latest Revision: 20230731
رمز التحديث: 20230731
مُعرف محوري في PubMed: PMC9615025
DOI: 10.1158/2767-9764.crc-22-0314
PMID: 36311816
قاعدة البيانات: MEDLINE
الوصف
تدمد:2767-9764
DOI:10.1158/2767-9764.crc-22-0314