남도현 교수

(SAIHST 융합의과학과 학과장)

Impact Factor ('14) = 29.352

Nat Genet. 2016 Jun 6. doi: 10.1038/ng.3590. [Epub ahead of print] 

http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3590.html

 

Clonal evolution of glioblastoma under therapy.

Wang J, Cazzato E, Ladewig E, Frattini V, Rosenbloom DI, Zairis S, Abate F, Liu Z, Elliott O, Shin YJ, Lee JK, Lee IH, Park WY, Eoli M, Blumberg AJ, Lasorella A, Nam DH, Finocchiaro G, Iavarone A, Rabadan R.
 

Abstract

 

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. To better understand how GBM evolves, we analyzed longitudinal genomic and transcriptomic data from 114 patients. The analysis shows a highly branched evolutionary pattern in which 63% of patients experience expression-based subtype changes. The branching pattern, together with estimates of evolutionary rate, suggests that relapse-associated clones typically existed years before diagnosis. Fifteen percent of tumors present hypermutation at relapse in highly expressed genes, with a clear mutational signature. We find that 11% of recurrence tumors harbor mutations in LTBP4, which encodes a protein binding to TGF-β. Silencing LTBP4 in GBM cells leads to suppression of TGF-β activity and decreased cell proliferation. In recurrent GBM with wild-type IDH1, high LTBP4 expression is associated with worse prognosis, highlighting the TGF-β pathway as a potential therapeutic target in GBM.

 

    (출처_PUBMED)

남도현 교수 연구소개 [프로필 보기]

 현대의학이 눈부신 발전을 이룩하고 있지만 아직 암은 대표적인 난치성 질환 중 하나이다. 또한 기존 치료법에 내성을 보이는 경우가 많아 새로운 개념의 항암치료법 개발이 절실히 요구되고 있다. 이에 본 연구진에서는 항암치료 내성을 가진 암줄기세포를 표적으로 하여, 암줄기세포의 표지자 및 특정 신호전달체계와 유전자 발현의 특성에 대한 연구를 진행하고 있으며, 이러한 연구의 결과들은 유수의 저널에 게재되어 세계적으로 주목을 받고 있다. 특히, 2005년 교모세포종 환자로의 암줄기세포 분리·배양법을 국내 최초로 확립한 이후, 다양한 암환자로부터 유래한 세포 라이브러리를 구축하고 있으며, 이는 암환자의 발암 기전에 대한 충분한 리소스를 제공함으로써 기초연구와 임상을 연결하는 중개연구에 필수적인 한 축을 담당하고 있다. 이와 더불어, 본 연구진에서는 암줄기세포 연구와 인체 유래 조직을 이용한 유전체 연구를 결합하여 환자를 대변할 수 있는 전임상 모델(아바타 마우스) 및 유전체 분석 데이터를 활용한 환자 맞춤형 약물개발 스크리닝 플랫폼(아바타 스캔시스템)을 구축 하였으며, 유전체 기반의 개인맞춤 항암치료법 개발을 위한 연구를 진행하고 있다.