Clinical Implication of CDH1 Mutations in Genetic Testing for Diffuse Gastric Cancer Patients.

IF 2.5 3区医学 Q3 ONCOLOGY

Oncology Pub Date : 2024-01-01 Epub Date: 2023-09-19 DOI:10.1159/000533774

Giovanni Corso, Cristina Maria Trovato, Salvatore Petitto, Antonia Girardi, Alessandra Margherita De Scalzi, Beatrice Bianchi, Francesca Magnoni, Antonio Cioffi, Viviana Galimberti, Paolo Veronesi, Giovanni Mazzarol, Patrick Maisonneuve

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引用次数: 0

Abstract

Introduction: The objective of this study was to reclassify published germline CDH1 variants identified in gastric cancer (GC) in accordance with the latest ClinVar definition and to correlate their pathogenicity with the established international clinical criteria for genetic testing.

Methods: The relevant literature dating from 1998 to 2019 was systematically searched for data on CDH1 germline mutations in accord with PRISMA guidelines. The collected variants were classified according to the latest ClinVar definition into the following classes: benign (B), likely benign (LB), pathogenic (P), likely pathogenic (LP), and variant of unknown significance (VUS). The McNemar test was used to compare the adequacy of current versus previous International GC Linkage Consortium (IGCLC) criteria.

Results: We reclassified a total of 247 CDH1 variants, and we identified that about 70% of B/LB variant carriers were not fulfilling the defined clinical criteria. Instead, all P/LP variants (100%) were associated with the hereditary diffuse gastric cancer (HDGC) phenotype fulfilling the 2020 ILGCC criteria, with a significant improvement (p = 0.025) compared to previous version.

Conclusions: We conclude that germline CDH1 genetic testing is indicated only in families meeting the clinical criteria for the HDGC syndrome. This observation suggests that clinical phenotypes that do not clearly fulfill these criteria should not be considered for CDH1 genetic testing.

查看原文本刊更多论文

CDH1突变在弥漫性癌症患者基因检测中的临床意义。

简介：本研究的目的是根据最新的ClinVar定义，对已发表的癌症（GC）种系CDH1变体进行重新分类，并将其致病性与已建立的国际基因检测临床标准相关联。方法：根据PRISMA指南，系统检索1998年至2019年的相关文献中CDH1种系突变的数据。根据最新的ClinVar定义，将收集到的变异分为以下几类：良性（B）、可能良性（LB）、致病性（P）、可能致病性（LP）和意义未知的变异（VUS）。Mc-Nemar检验用于比较当前与先前国际GC链接联盟（IGCLC）标准的充分性。结果：我们对总共247种CDH1变体进行了重新分类，我们发现大约70%的B/LB变体携带者不符合规定的临床标准。相反，所有P/LP变体（100%）与符合2020 ILGCC标准的遗传性弥漫性癌症（HDGC）表型相关，与先前版本相比有显著改善（P=0.025）。结论：我们的结论是，种系CDH1基因检测仅适用于符合HDGC综合征临床标准的家庭。这一观察结果表明，不明确满足这些标准的临床表型不应被考虑用于CDH1基因检测。

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

Oncology 医学-肿瘤学

CiteScore

6.00

自引率

2.90%

发文量

审稿时长

6-12 weeks

期刊介绍： Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.