Shuhua Zheng, Yirong Liu, Paul D. Kinkopf, Amulya Yalamanchili, Jonathan B. Strauss, Eric D. Donnelly
{"title":"Whole exome sequencing of low risk endometrial cancer patients with isolated local recurrences","authors":"Shuhua Zheng, Yirong Liu, Paul D. Kinkopf, Amulya Yalamanchili, Jonathan B. Strauss, Eric D. Donnelly","doi":"10.1016/j.ctarc.2025.100890","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>A small proportion of clinicopathologically low-risk endometrial cancer (EC) patients who omitted adjuvant radiotherapy (RT) may subsequently develop a local recurrence. Molecular profile for those clinically low-risk yet recurred EC patients is unavailable.</div></div><div><h3>Methods</h3><div>A total of 442 EC patients treated from 2014 to 2020 at Northwestern Memorial Hospital were studied. Among them, 28 patients clinically low risk or low-intermediate risk per GOG-99 criteria developed an isolated local recurrence after hysterectomy, bilateral salpingo-oophorectomy, and omitted RT. Whole exome sequencing (WES) was performed on 22 patients whose pathologic specimen were retrievable.</div></div><div><h3>Results</h3><div>The majority of the cases studied were molecularly No Specific Molecular Profile (NSMP) cohort (91%). We identified <em>CTNNB1, FGFR2, PTEN</em>, and <em>KRAS</em> as the most frequently altered pathogenic or likely pathogenic genes with 5 (22.7%), 5 (22.7%), 4 (18.2%), and 3 (13.6%) out of 22 patients carrying these alterations, respectively. <em>TP53</em> somatic alterations were identified in 2 (9.1%) out of 22 cases. Analysis of The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) dataset identified 53 EC patients with pathologically Grade 1 molecularly NSMP cohort. Within this cohort, <em>CTNNB</em>1 alterations were identified in 31 patients (58%) and prognosticated worse progression free survival (<em>p</em><0.05).</div></div><div><h3>Conclusion</h3><div>NSMP molecular group constitutes the majority of clinically low-risk EC patients with isolated local recurrences. The <em>CTNNB1</em> alteration was validated as a biomarker in prognostication in this independent cohort and may help guide adjuvant treatment decisions.</div></div>","PeriodicalId":9507,"journal":{"name":"Cancer treatment and research communications","volume":"43 ","pages":"Article 100890"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer treatment and research communications","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2468294225000280","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction
A small proportion of clinicopathologically low-risk endometrial cancer (EC) patients who omitted adjuvant radiotherapy (RT) may subsequently develop a local recurrence. Molecular profile for those clinically low-risk yet recurred EC patients is unavailable.
Methods
A total of 442 EC patients treated from 2014 to 2020 at Northwestern Memorial Hospital were studied. Among them, 28 patients clinically low risk or low-intermediate risk per GOG-99 criteria developed an isolated local recurrence after hysterectomy, bilateral salpingo-oophorectomy, and omitted RT. Whole exome sequencing (WES) was performed on 22 patients whose pathologic specimen were retrievable.
Results
The majority of the cases studied were molecularly No Specific Molecular Profile (NSMP) cohort (91%). We identified CTNNB1, FGFR2, PTEN, and KRAS as the most frequently altered pathogenic or likely pathogenic genes with 5 (22.7%), 5 (22.7%), 4 (18.2%), and 3 (13.6%) out of 22 patients carrying these alterations, respectively. TP53 somatic alterations were identified in 2 (9.1%) out of 22 cases. Analysis of The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) dataset identified 53 EC patients with pathologically Grade 1 molecularly NSMP cohort. Within this cohort, CTNNB1 alterations were identified in 31 patients (58%) and prognosticated worse progression free survival (p<0.05).
Conclusion
NSMP molecular group constitutes the majority of clinically low-risk EC patients with isolated local recurrences. The CTNNB1 alteration was validated as a biomarker in prognostication in this independent cohort and may help guide adjuvant treatment decisions.
期刊介绍：
Cancer Treatment and Research Communications is an international peer-reviewed publication dedicated to providing comprehensive basic, translational, and clinical oncology research. The journal is devoted to articles on detection, diagnosis, prevention, policy, and treatment of cancer and provides a global forum for the nurturing and development of future generations of oncology scientists. Cancer Treatment and Research Communications publishes comprehensive reviews and original studies describing various aspects of basic through clinical research of all tumor types. The journal also accepts clinical studies in oncology, with an emphasis on prospective early phase clinical trials. Specific areas of interest include basic, translational, and clinical research and mechanistic approaches; cancer biology; molecular carcinogenesis; genetics and genomics; stem cell and developmental biology; immunology; molecular and cellular oncology; systems biology; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; cancer policy; and integration of various approaches. Our mission is to be the premier source of relevant information through promoting excellence in research and facilitating the timely translation of that science to health care and clinical practice.
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