Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK, OX3 7LE, UK.
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, 324, Rome, 00161, Italy.
Endocrine. 2018 Jan;59(1):175-182. doi: 10.1007/s12020-017-1310-9. Epub 2017 May 5.
Several new gene mutations have been reported in recent years to be associated with a risk of familial pheochromocytoma. However, it is unclear as to whether extensive genetic testing is required in all patients.
The clinical data of consecutive patients operated for pheochromocytoma over a decade in a tertiary referral center were reviewed. Genetic screening was performed using a 10-gene panel: RET, VHL, SDHB, SDHD, SDHA, SDHC, SDHAF2, MAX, TMEM127 and FH.
A total of 166 patients were analyzed: 87 of them had genetic screening performed (39 M: 44.8%, 48 F: 55.2%, age range 6-81 years, mean 45±16.8 years). In total, 22/87 (25.3%) patients had germline mutations, while 65/87 (74.7%) patients presented with apparently sporadic tumors. Germline VHL mutations were identified in 11.7% of patients, RET in 6.8% (five MEN2A/MEN2 and one MEN2B/MEN3), SDHD in 2.3%, MAX in 2.3%, SDHB in 1.1%, and TMEM127 in 1.1% of patients. At diagnosis, 15.1% of patients with unilateral non-syndromic pheochromocytoma showed germline mutations. We identified 19.7% of mutations in patients with unilateral-non-recurrent pheochromocytomas within 5 years vs. 50% in the recurrent-bilateral-metastatic group (p = 0.01). Germline mutations were more frequently seen with bilateral pheochromocytomas (p = 0.001): 80% of patients with bilateral disease had germline mutations (4 VHL, 3 RET, 1 MAX).
The advent of rapid genetic screening using a gene-panel makes it feasible to screen large cohorts of patients and provides a valuable tool to contribute to the prediction of bilateral and malignant disease and to screen family members.
近年来，已有报道称几种新的基因突变与家族性嗜铬细胞瘤的风险相关。然而，目前尚不清楚是否需要对所有患者进行广泛的基因检测。
对一家三级转诊中心十年来连续接受嗜铬细胞瘤手术的患者的临床资料进行了回顾性分析。采用 10 个基因panel（RET、VHL、SDHB、SDHD、SDHA、SDHC、SDHAF2、MAX、TMEM127 和 FH）进行基因筛查。
共分析了 166 例患者：其中 87 例进行了基因筛查（男性 39 例：44.8%，女性 48 例：55.2%，年龄 6-81 岁，平均 45±16.8 岁）。总共发现 22/87（25.3%）例患者存在种系突变，而 65/87（74.7%）例患者表现为明显的散发性肿瘤。VHL 基因突变见于 11.7%的患者，RET 基因突变见于 6.8%（5 例 MEN2A/MEN2 和 1 例 MEN2B/MEN3），SDHD 基因突变见于 2.3%，MAX 基因突变见于 2.3%，SDHB 基因突变见于 1.1%，TMEM127 基因突变见于 1.1%的患者。在诊断时，15.1%单侧非综合征性嗜铬细胞瘤患者存在种系突变。我们发现单侧非复发性嗜铬细胞瘤患者在 5 年内的突变率为 19.7%，而复发性双侧转移性患者的突变率为 50%（p=0.01）。种系突变更常见于双侧嗜铬细胞瘤（p=0.001）：80%双侧疾病患者存在种系突变（4 例 VHL、3 例 RET、1 例 MAX）。
使用基因panel 进行快速基因筛查的出现使得对大量患者进行筛查成为可能，并为预测双侧和恶性疾病以及筛查家庭成员提供了有价值的工具。
