Genetic testing in pheochromocytomas/ paragangliomas (including tentative study NGS)in Japan.

• Project/Area Number: 16K08961
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: University of Tsukuba
• Principal Investigator: kawakami yasushi 筑波大学, 医学医療系, 教授 (70234028)
• Co-Investigator(Kenkyū-buntansha): 竹越 一博 筑波大学, 医学医療系, 教授 (40261804)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 褐色細胞腫 / 次世代シークエンサー / 遺伝子パネル / 遺伝子診断 / SDHB変異 / 悪性化 / ＮＧＳ

Outline of Final Research Achievements

Introduction: Great progress has been achieved in the fields, especially genetics in pheochromocytomas/ paragangliomas . Major aim of this study is to investigate genetic back ground in Japan.Results: 1) We have carried out genetic testing in 398 cases in Japan. In 340 index cases, we found 130 cases whose genetic mutations are positive and summarized herein : SDHB 54 cases, SDHD 32 cases, VHL 20 cases, RET 8 cases, TMEM 127 7 cases, MAX 6 cases.Consequently, notably high degree (130/340=38.2%) of patients carry genetic mutation, similar to those of previous reports from USA and Europe.
2) Growing evidence suggest that mutation of SDHB is highly associated with abdominal paraganglioma and the following distant metastasis.
In the present study, analysis of blood taken from 57 cases of malignant pheochromocytomas in Japanese subjects led to the identification of 17 SDHB mutations（20/57=35.1％).

Academic Significance and Societal Importance of the Research Achievements

筑波大学で解析を施行したpheochromocytoma/ paraganglioma の2007年から2019年４月までの結果は以下の通りである。1）398例解析済みである。発端者340例中変異陽性は130例で，変異陽性率は38.2％(130/340)（内訳:SDHB.54例，SDHD.32例，VHL.20例，SDHC.2例，SDHA.1例，RET.8例，TMEM1127.7例，MAX.6例）。2）SDHB変異陽性患者49例中54例が腹部パラガングリオ－マが初発（90.7％）であり、悪性化した例が20例（20/54＝37.0％）であった。

Research Products

• [Journal Article] A synonymous VHL variant in exon 2 confers susceptibility to familial pheochromocytoma and von Hippel-Lindau disease. (2019)
  • Author(s): Flores SK, Cheng Z, Jasper AM, Natori K, Okamoto T, Tanabe A, Gotoh K, Shibata H, Sakurai A, Nakai T, Wang X, Zethoven M, Balachander S, Aita Y, Young W, Zheng S, Takekoshi K, Nakamura E, Tothill RW, Aguiar RCT, Dahia PLM
  • Journal Title: J Clin Endocrinol Metab Volume: in press Issue: 9 Pages: 3826-3834
  • DOI: 10.1210/jc.2019-00235
  • Peer Reviewed / Open Access / Int'l Joint Research