Molecular Classification of Endometrial Cancers Using an Integrative DNA Sequencing Panel.

IF 2 3区医学 Q3 ONCOLOGY

Journal of Surgical Oncology Pub Date : 2024-11-05 DOI:10.1002/jso.27973

Soyoun R Kim, Leslie Oldfield, Raymond H Kim, Osvaldo Espin-Garcia, Kathy Han, Danielle Vicus, Lua Eiriksson, Alicia Tone, Aaron Pollett, Matthew Cesari, Blaise Clarke, Marcus Q Bernardini, Trevor J Pugh, Sarah E Ferguson

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引用次数: 0

Abstract

Background and objectives: Adoption of molecular classification in endometrial cancer (EC) into clinical practice remains challenging due to complexity in coordination of multiple assays. We aimed to develop a simple molecular technique to classify ECs into four subgroups using our custom-designed targeted sequencing panel.

Methods: Patients with newly diagnosed ECs were prospectively recruited from three cancer centres in Ontario, Canada. Using our panel, 181 ECs were sequenced. Variants were analysed for pathogenicity and clinicopathologic information was collected through medical records retrospectively.

Results: Of 181, 86 (48%) were mismatch repair deficient (MMRd), of which 62 (72%) harboured MLH1 promoter methylation and 24 (28%) had pathogenic variants in MMR genes. Of single classifiers, three (1.8%) had pathogenic POLE (POLEmut), 15 (9%) had TP53 mutations (p53abn) and 61 (37%) had no specific molecular profile subtype (NSMP). Sixteen (9%) had more than one molecular classifying feature, with eight (4%) MMRd-p53abn, six (3%) POLEmut-MMRd, one (0.5%) POLEmut-MMRd-p53abn and one (0.5%) POLEmut-p53abn. When MMRd group was further subclassified according to mechanism of MMR loss, MLH1 promoter methylated group had worse outcomes than those with somatic MMR pathogenic variants.

Conclusions: Our panel can classify ECs into four subgroups through a simplified process and can be implemented reflexively in clinical practice.

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使用整合 DNA 测序面板对子宫内膜癌进行分子分类。

背景和目的：在临床实践中采用子宫内膜癌（EC）分子分类仍具有挑战性，因为多种检测方法的协调非常复杂。我们旨在开发一种简单的分子技术，利用我们定制设计的靶向测序面板将子宫内膜癌分为四个亚组：方法：我们从加拿大安大略省的三个癌症中心招募了新诊断出的EC患者。使用我们的测序板对 181 例心肌梗死患者进行了测序。对变异进行致病性分析，并通过病历回顾性收集临床病理信息：结果：181例EC中，86例（48%）存在错配修复缺陷（MMRd），其中62例（72%）存在MLH1启动子甲基化，24例（28%）存在MMR基因致病变异。在单一分类中，3 例（1.8%）有致病性 POLE（POLEmut），15 例（9%）有 TP53 突变（p53abn），61 例（37%）无特定分子特征亚型（NSMP）。16人（9%）具有一种以上的分子分类特征，其中8人（4%）为MMRd-p53abn，6人（3%）为POLEmut-MMRd，1人（0.5%）为POLEmut-MMRd-p53abn，1人（0.5%）为POLEmut-p53abn。当根据MMR丧失的机制对MMRd组进行进一步细分时，MLH1启动子甲基化组的预后比具有体细胞MMR致病变异的组更差：结论：我们的小组可通过简化流程将心肌梗死分为四个亚组，并可在临床实践中灵活应用。

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

Journal of Surgical Oncology 医学-外科

CiteScore

4.70

自引率

4.00%

发文量

367

审稿时长

2 months

期刊介绍： The Journal of Surgical Oncology offers peer-reviewed, original papers in the field of surgical oncology and broadly related surgical sciences, including reports on experimental and laboratory studies. As an international journal, the editors encourage participation from leading surgeons around the world. The JSO is the representative journal for the World Federation of Surgical Oncology Societies. Publishing 16 issues in 2 volumes each year, the journal accepts Research Articles, in-depth Reviews of timely interest, Letters to the Editor, and invited Editorials. Guest Editors from the JSO Editorial Board oversee multiple special Seminars issues each year. These Seminars include multifaceted Reviews on a particular topic or current issue in surgical oncology, which are invited from experts in the field.