Abstract
Background
Temporal bone paragangliomas are rare tumours with variable presentation that can be hereditary. Identification of clinical and genetic factors of aggressive tumour behaviour is important.
Objective
To determine the underlying genetic mutations and genotype/phenotype correlations in a multi-ethnic population of South Florida with sporadic temporal bone paragangliomas.
Methods
In a cohort of glomus tympanicum (GT) and glomus jugulare (GJ) cases, we assessed the frequency of pathogenic single nucleotide variants, insertions, deletions, and duplications in coding exons of genes that have been associated with paragangliomas (SDHB, SDHC, SDHD, SDHA, SDHAF2, RET, NF1, VHL, TMEM127, and MAX).
Results
None of the 12 GT cases had mutations. Among 13 GJ cases, we identified four mutation carriers (31%); two in SDHC, one in SDHB, and one in SDHD. All patients with pathogenic mutations were of Hispanic ethnicity, presented at a younger age (mean 27.5 versus 52.11 years), and with more advanced disease when compared to mutation-negative GJ cases.
Conclusions and Significance: Mutations in the SDH genes are found in 31% of sporadic GJ. SDH-associated GJ had advanced disease and a 50% risk of metastasis. Our data supports emerging recommendations for genetic screening in all populations with GJ tumours as the genetic status informs management.
Chinese Abstract
背景:颞骨副神经节瘤是一种罕见的肿瘤。它具有多种表现, 并可能有遗传性。鉴定 侵袭性肿瘤行为的临床和遗传因素很重要。
目的:确定南佛罗里达州的患有散发性颞骨副神经节瘤的多种族人群的潜在基因突变和基因型/表型相关性。
方法:在一组鼓室球 (GT) 和颈静脉球 (GJ) 病例中, 我们评估了与副神经节瘤相关的基因编码外显子中致病性单核苷酸变异、插入、缺失和重复的频率(SDHB、SDHC、SDHD、SDHA、SDHAF2、RET、NF1、VHL、TMEM127 和 MAX)。
结果:12例GT病例均无突变。 在 13 个 GJ 病例中, 发现有四个突变载体(31%); 两个在 SDHC 中, 一个在 SDHB 中, 一个在 SDHD 中。 所有致病突变患者都是西班牙裔, 发病年龄较小(平均 27.5 岁相较于 52.11 岁), 并且与突变阴性 GJ 病例相比, 疾病属更晚期。
结论和意义:在 31% 的散发性 GJ 中发现 SDH 基因突变。SDH 相关的 GJ 病例属晚期和 并有50% 的转移风险。 我们的数据支持这样的建议:对所有 GJ 肿瘤人群进行遗传筛查, 因为遗传状态可以给疾病管理提供信息。
Disclosure statement
The authors report no conflicts of interest.