The clinical genetics of phaeochromocytoma and paraganglioma

ABSTRACT Phaeochromocytoma and paraganglioma are rare catecholamine-producing tumours, recognised to have one of the richest hereditary backgrounds of all neoplasms, with germline mutations seen in approximately 30% of patients. They can be a part of genetic syndromes such as MEN 2 or Neurofibromatosis type 1, or can be found as apparently sporadic tumours. Germline mutations are almost always found in syndromic patients. Nonetheless, apparently sporadic phaeochromocytoma too show high germline mutation rates. Early detection of a genetic mutation can lead to early diagnosis of further tumours via surveillance, early treatment and better prognosis. Apart from this, the genetic profile has important relevance for tumour location and biochemical profile, and can be a useful predictor of future tumour behaviour. It also enables family screening and surveillance. Moreover, recent studies have demonstrated significant driver somatic mutations in up to 75% of all tumours. Arch Endocrinol Metab. 2017;61(5):490-500

【摘要】嗜铬细胞瘤（Phaeochromocytoma）与副神经节瘤（Paraganglioma）是一类罕见的儿茶酚胺分泌性肿瘤，被认为是所有肿瘤中遗传背景最为丰富的肿瘤类型之一，约30%的患者可检出种系突变（germline mutations）。此类肿瘤可作为多发性内分泌腺瘤综合征2型（MEN 2）、1型神经纤维瘤病（Neurofibromatosis type 1）等遗传综合征的临床表现，也可表现为外观无明显遗传背景的散发性肿瘤（sporadic tumours）。种系突变几乎仅见于综合征相关患者，但即便看似散发性的嗜铬细胞瘤，其种系突变率也处于较高水平。早期检出遗传突变可通过随访监测实现继发肿瘤的早期诊断、早期治疗并改善患者预后。此外，肿瘤的遗传特征与肿瘤发生部位及生化表型密切相关，可有效预测肿瘤的后续生物学行为，同时可为家族成员的筛查与随访提供依据。近期研究证实，在高达75%的此类肿瘤中可检出重要的驱动性体细胞突变（somatic mutations）。本文摘自《内分泌代谢档案》（Arch Endocrinol Metab.）2017年；61(5):490-500