台灣副神經節瘤的資料庫建立以及次世代定序基因檢測

Abstract

副神經節瘤是起源於嗜鉻細胞的罕見神經內分泌腫瘤,嗜鉻細胞存在於身體各部位,主要腫瘤發生在腎上腺髓質,另少部份發生於腹部、胸部、骨盆和頸部。當副神經節瘤分泌過量的兒茶酚胺,會引發一些症狀,例如頭痛、心悸、出汗或心血管相關併發症等等,這些症狀通常也伴隨著高血壓。但也有約5%的患者無任何症狀,透過健檢的腹部超音波才發現。 副神經節瘤具有很強的遺傳性,約有4成為遺傳性遺傳, 4成為體細胞突變,目前文獻發現會造成副神經節瘤,已經至少確定了21個驅動基因,針對不同的基因變異,其預後以及轉移的風險性具有極大的差異,因此建議所有患者進行基因檢測與遺傳諮詢。 本研究收入了曾於臺大醫院看診的副神經節瘤個案共139位。將這些個案的家族史、基因檢測、生化檢測數值等資訊,統整臺灣本土副神經節瘤疾病的資料,並在臺大安全網域下建立線上REDCap資料庫。 在本研究臨床確診為副神經節瘤的家族中,次世代定序基因檢測確診,血液檢體共108位,檢出遺傳性突變為32.4%。腫瘤檢體共32件,扣除找到遺傳性突變之個案,檢出體細胞突變為40%。

Paraganglioma is a rare neuroendocrine tumor originating from chromaffin cells. Chromaffin cells are present in various parts of the body. The main tumor occurs in the adrenal medulla. Paraganglioma occurs rarely in the abdomen, chest, pelvis and neck. When paraganglioma secretes excessive amounts of catecholamines, they could cause symptoms such as headaches, palpitations, sweating, or cardiovascular-related complications. These symptoms are often accompanied by high blood pressure. However, about 5% of patients have no symptoms and are only discovered through abdominal ultrasound during physical examination.

Paragangliomas are highly heritable, with approximately 40% of cases being germline inheritance and 40% being somatic mutations. Current literatures have found that at least 21 driver genes have been identified that could cause paraganglioma. Given the heterogeneous clinical behavior and variable metastatic potential depend on specific genetic mutations, genetic testing and genetic counseling are recommended for all patients.

This study includes a total cohort of 139 paraganglioma patients that had been treated at National Taiwan University Hospital. Collation of the family history, genetic testing, biochemical test values and other information of these cases were integrated with the paraganglioma disease data in Taiwan, and an online REDCap database was established under the secure network of National Taiwan University.

Among the families with clinically diagnosed paraganglioma in this study, next-generation sequencing gene testing confirmed the diagnosis. A total of 108 blood samples were collected, and 32.4% of the germline mutations were detected. There were 32 tumor specimens, and somatic mutation in patients without germline mutation is 40%.