Testing for germline mutations in sporadic pheochromocytoma/paraganglioma: a systematic review
Testing for germline mutations in sporadic pheochromocytoma/paraganglioma: a systematic review
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DOI：
10.1111/cen.12530
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发表时间：
2015-03-01
影响因子：
3.2
通讯作者：
Murad, Mohammad H.
中科院分区：
文献类型：
--
作者：
Brito, Juan P.;Asi, Noor;Murad, Mohammad H.
背景：散发性嗜铬细胞瘤和副神经节瘤(SPPs)中胚系突变的存在可能会改变患者及其家属的临床治疗。目的描述种系突变在SPP中的频率，并确定这些突变的检测指标在患者及其家庭成员中的价值。方法检索数据库至2012年6月，对SPP患者进行种系基因检测。用于定义散发性肿瘤的标准是：(I)没有PCC/PG家族史，(Ii)没有症状特征，(Iii)没有双侧疾病，(Iv)没有转移性疾病。这些患者接受了SDHAF2、RET、SDHD、SDHB、SDHC、VHL、TMEM127、MAX、异柠檬酸脱氢酶突变(IDH)和NF1的检测。SPP中胚系突变的总频率为5031例中的551例，或11%；当对符合散发性肿瘤四项标准的患者进行研究时，该频率为1332例中的171例，或13%。最常见的种系突变是3611例中的SDHB167例(46%)。几乎没有结果数据可用于评估基因检测在指标病例和家庭成员中的益处。结论SPP中种系突变的频率约为11-13%，最常见的突变影响不到20例患者中的1例。对SPP患者及其家人进行种系突变检测的价值尚不清楚，因为潜在的益处和危害的平衡仍不清楚。
BackgroundThe presence of germline mutations in sporadic pheochromocytomas and paragangliomas (SPPs) may change the clinical management of both index patients and their family members. However, the frequency of germline mutations in SPPs is unknown.ObjectiveTo describe the frequency of germline mutations in SPPs and to determine the value of testing index patients and their family members for these mutations.MethodsWe searched databases through June 2012 for observational studies of patients with SPPs who underwent germline genetic testing. The criteria used to define sporadic tumours were (i) the absence of a family history of PCC/PG, (ii) the absence of syndromic features, (iii) the absence of bilateral disease and (iv) the absence of metastatic disease.ResultsWe included 31 studies including 5031 patients (mean age 44). These patients received tests for any of these ten mutations: SDHAF2, RET, SDHD, SDHB, SDHC, VHL, TMEM127, MAX, Isocitrate Dehydrogenase Mutation (IDH) and NF1. The overall frequency of germline mutation in SPP was 551 of 5031 or 11%; when studies with patients fulfilling four criteria for sporadic tumours were used, the frequency was 171 of 1332 or 13%. The most common germline mutation was SDHB 167 of 3611 (46%). Little outcome data were available to assess the benefits of genetic testing in index cases and family members.ConclusionsThe frequency of germline mutations in SPPs is approximately 11-13% and the most common mutations affect less than 1 in 20 patients. The value of testing for germline mutations in patients with SPPs and their family members is unknown, as the balance of potential benefits and harms remains unclear.