HUN-REN Hereditary Tumors Research Group, Hungarian Research Network, H-1089 Budapest, Hungary.
Department of Laboratory Medicine, Semmelweis University, H-1089 Budapest, Hungary.
J Clin Endocrinol Metab. 2024 Nov 18;109(12):3220-3233. doi: 10.1210/clinem/dgae300.
Heterogenous clinical manifestations, overlapping phenotypes, and complex genetic backgrounds are common in patients with endocrine tumors. There are no comprehensive recommendations for genetic testing and counseling of these patients compared to other hereditary cancer syndromes. The application of multigene panel testing is common in clinical genetic laboratories, but their performance for patients with endocrine tumors has not been assessed.
As a national reference center, we prospectively tested the diagnostic utility and cost-efficiency of a multigene panel covering 113 genes representing genetic susceptibility for solid tumors; 1279 patients (including 96 cases with endocrine tumors) were evaluated between October 2021 and December 2022 who were suspected to have hereditary tumor syndromes.
The analytical performance of the hereditary cancer panel was suitable for diagnostic testing. Clinical diagnosis was confirmed in 24% (23/96); incidental findings in genes not associated with the patient's phenotype were identified in 5% (5/96). A further 7% of pathogenic/likely pathogenic variants were detected in genes with potential genetic susceptibility roles but currently no clear clinical consequence. Cost-benefit analysis showed that the application of a more comprehensive gene panel in a diagnostic laboratory yielded a shorter turnaround time and provided additional genetic results with the same cost and workload.
Using comprehensive multigene panel results in faster turnaround time and cost-efficiently identifies genetic alterations in hereditary endocrine tumor syndromes. Incidentally identified variants in patients with poor prognoses may serve as a potential therapeutic target in tumors where therapeutic possibilities are limited.
内分泌肿瘤患者的临床表现异质性、表型重叠和复杂的遗传背景较为常见。与其他遗传性癌症综合征相比，针对这些患者的基因检测和咨询尚无全面建议。多基因面板检测在临床遗传实验室中应用广泛，但尚未评估其在内分泌肿瘤患者中的性能。
作为国家参考中心，我们前瞻性地测试了涵盖代表实体瘤遗传易感性的 113 个基因和 1279 名患者（包括 96 例内分泌肿瘤患者）的多基因面板的诊断效用和成本效益，这些患者疑似患有遗传性肿瘤综合征。
遗传性癌症面板的分析性能适合诊断测试。临床诊断在 24%（23/96）的患者中得到证实；在 5%（5/96）的患者中发现了与患者表型无关的基因中的偶然发现。在具有潜在遗传易感性作用但目前尚无明确临床后果的基因中，还检测到 7%的致病性/可能致病性变异。成本效益分析表明，在诊断实验室中应用更全面的基因面板可以缩短周转时间，并以相同的成本和工作量提供额外的遗传结果。
使用全面的多基因面板可以更快地获得结果，并且具有成本效益，可以识别遗传性内分泌肿瘤综合征中的遗传改变。在预后较差的患者中偶然发现的变异可能成为治疗可能性有限的肿瘤中的潜在治疗靶点。
