Gargallo Pablo, Oltra Silvestre, Yáñez Yania, Juan-Ribelles Antonio, Calabria Inés, Segura Vanessa, Lázaro Marián, Balaguer Julia, Tormo Teresa, Dolz Sandra, Fernández José María, Fuentes Carolina, Torres Bárbara, Andrés Mara, Tasso María, Castel Victoria, Font de Mora Jaime, Cañete Adela
Pediatric Oncology Department, Hospital Universitario y Politécnico La Fe de Valencia, 46026 Valencia, Spain.
Imegen-Health in Code Group, Department of Oncology, Paterna, 46980 Valencia, Spain.
Cancers (Basel). 2021 Oct 24;13(21):5339. doi: 10.3390/cancers13215339.
Knowledge about genetic predisposition to pediatric cancer is constantly expanding. The categorization and clinical management of the best-known syndromes has been refined over the years. Meanwhile, new genes for pediatric cancer susceptibility are discovered every year. Our current work shares the results of genetically studying the germline of 170 pediatric patients diagnosed with cancer. Patients were prospectively recruited and studied using a custom panel, . The well-categorized predisposing syndromes incidence was 9.4%. Likely pathogenic variants for predisposition to the patient's tumor were identified in an additional 5.9% of cases. Additionally, a high number of pathogenic variants associated with recessive diseases was detected, which required family genetic counseling as well. The clinical utility of the Jongmans MC tool was evaluated, showing a high sensitivity for detecting the best-known predisposing syndromes. Our study confirms that the Jongmans MC tool is appropriate for a rapid assessment of patients; however, the updated version of Ripperger T criteria would be more accurate. Meaningfully, based on our findings, up to 9.4% of patients would present genetic alterations predisposing to cancer. Notably, up to 20% of all patients carry germline pathogenic or likely pathogenic variants in genes related to cancer and, thereby, they also require expert genetic counseling. The most important consideration is that the detection rate of genetic causality outside Jongmans MC et al. criteria was very low.
关于儿童癌症遗传易感性的知识正在不断扩展。多年来，对最知名综合征的分类和临床管理已得到完善。与此同时，每年都有新的儿童癌症易感基因被发现。我们目前的工作分享了对170名被诊断患有癌症的儿科患者的生殖系进行基因研究的结果。患者是前瞻性招募的，并使用定制的基因检测板进行研究。分类明确的易感综合征发病率为9.4%。在另外5.9%的病例中鉴定出了可能导致患者肿瘤易感性的致病变异。此外，还检测到大量与隐性疾病相关的致病变异，这也需要进行家族遗传咨询。对Jongmans MC工具的临床效用进行了评估，结果显示其对检测最知名的易感综合征具有较高的敏感性。我们的研究证实，Jongmans MC工具适用于对患者进行快速评估；然而，Ripperger T标准的更新版本会更准确。有意义的是，根据我们的研究结果，高达9.4%的患者会出现导致癌症的基因改变。值得注意的是，所有患者中高达20%在与癌症相关的基因中携带生殖系致病或可能致病的变异，因此，他们也需要专家遗传咨询。最重要的一点是，在Jongmans MC等人的标准之外，遗传因果关系的检测率非常低。
