Di Rado Sara, Giansante Roberta, Cicirelli Michela, Pilenzi Lucrezia, Dell'Elice Anastasia, Anaclerio Federico, Rimoldi Martina, Grassadonia Antonino, Grossi Simona, Canale Nicole, Ballerini Patrizia, Stuppia Liborio, Antonucci Ivana
Center for Advanced Studies and Technology (CAST), "G. D'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.
Department of Medical Genetics, "G. D'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.
Cancers (Basel). 2023 Dec 6;15(24):5730. doi: 10.3390/cancers15245730.
Several hereditary-familial syndromes associated with various types of tumors have been identified to date, evidencing that hereditary cancers caused by germline mutations account for 5-10% of all tumors. Advances in genetic technology and the implementation of Next-Generation Sequencing (NGS) have accelerated the discovery of several susceptibility cancer genes, allowing for the detection of cancer-predisposing mutations in a larger number of cases. The aim of this study is to highlight how the application of an NGS-multigene panel to a group of oncological patients subsequently leads to improvement in the identification of carriers of healthy pathogenic variants/likely pathogenic variants (PVs/LPVs) and prevention of the disease in these cases.
Starting from a total of 110 cancer patients carrying PVs/LPVs in genes involved in cancer susceptibility detected via a customized NGS panel of 27 cancer-associated genes, we enrolled 250 healthy collateral family members from January 2020 to July 2022. The specific PVs/LPVs identified in each proband were tested in healthy collateral family members via Sanger sequencing.
A total of 131 out of the 250 cases (52%) were not carriers of the mutation detected in the affected relative, while 119 were carriers. Of these, 81/250 patients carried PVs/LPVs on (33%), 35/250 harbored PVs/LPVs on other genes beyond and (14%), and 3/250 (1%) were PVs/LPVs carriers both on and on another susceptibility gene.
Our results show that the analysis of genes would have only resulted in a missed diagnosis in a number of cases and in the lack of prevention of the disease in a considerable percentage of healthy carriers with a genetic mutation (14%).
迄今为止，已确定了几种与各类肿瘤相关的遗传性家族综合征，这表明由种系突变引起的遗传性癌症占所有肿瘤的5%-10%。基因技术的进步和下一代测序（NGS）的应用加速了几种癌症易感基因的发现，使得在更多病例中能够检测到癌症易感性突变。本研究的目的是强调将NGS多基因检测应用于一组肿瘤患者如何随后改善对健康致病变异/可能致病变异（PVs/LPVs）携带者的识别，并在这些病例中预防疾病。
从通过定制的包含27个癌症相关基因的NGS检测发现携带癌症易感性相关基因中PVs/LPVs的110名癌症患者开始，我们在2020年1月至2022年7月期间招募了250名健康的旁系家庭成员。通过桑格测序在健康的旁系家庭成员中检测每个先证者中鉴定出的特定PVs/LPVs。
250例病例中共有131例（52%）不是受影响亲属中检测到的突变携带者，而119例是携带者。其中，81/250例患者在[具体基因]上携带PVs/LPVs（33%），35/250例在[具体基因]之外的其他基因上携带PVs/LPVs（14%），3/250例（1%）在[具体基因]和另一个易感基因上均为PVs/LPVs携带者。
我们的结果表明，对[具体基因]的分析在一些病例中只会导致漏诊，并且在相当比例的携带基因突变的健康携带者中（14%）无法预防疾病。
