Whole exome sequencing of low risk endometrial cancer patients with isolated local recurrences

Q3 Medicine

Cancer treatment and research communications Pub Date : 2025-01-01 DOI:10.1016/j.ctarc.2025.100890

Shuhua Zheng, Yirong Liu, Paul D. Kinkopf, Amulya Yalamanchili, Jonathan B. Strauss, Eric D. Donnelly

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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.

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孤立局部复发的低风险子宫内膜癌患者的全外显子组测序

一小部分临床病理低危的子宫内膜癌（EC）患者在省略辅助放疗（RT）后可能发生局部复发。临床低风险但复发的EC患者的分子谱尚不清楚。方法选取西北纪念医院2014 - 2020年收治的442例EC患者为研究对象。其中28例临床低风险或低-中风险（符合GOG-99标准）的患者在子宫切除术、双侧输卵管-卵巢切除术后出现局部孤立复发，省略rt。对22例可获得病理标本的患者进行全外显子组测序（WES）。结果绝大多数病例为分子无特异性分子谱（NSMP）队列（91%）。我们发现CTNNB1、FGFR2、PTEN和KRAS是最常改变的致病或可能致病基因，22例患者中分别有5例（22.7%）、5例（22.7%）、4例（18.2%）和3例（13.6%）携带这些基因改变。22例中有2例（9.1%）发现TP53体细胞改变。对癌症基因组图谱子宫体子宫内膜癌（TCGA-UCEC）数据集进行分析，确定了53例病理1级分子NSMP患者。在该队列中，31名患者（58%）发现CTNNB1改变，预后无进展生存期较差（p<0.05）。结论nsmp分子组在临床上局部孤立复发的低危EC患者中占多数。在这个独立的队列中，CTNNB1的改变被证实是一种预测预后的生物标志物，可能有助于指导辅助治疗决策。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer treatment and research communications Medicine-Oncology

CiteScore

4.30

自引率

0.00%

发文量

148

审稿时长

56 days

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.