Year: 2008
Type: article
Abstract: We have developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM), identifying frequent p18(INK4C) and p16(INK4A) codeletion. Functional reconstitution of p18(INK4C) in GBM cells null for both p16(INK4A) and p18(INK4C) resulted in impaired cell-cycle progression and tumorigenic potential. Conversely, RNAi-mediated depletion of p18(INK4C) in p16(INK4A)-deficient primary astrocytes or established GBM cells enhanced tumorigenicity in vitro and in vivo. Furthermore, acute suppression of p16(INK4A) in primary astrocytes induced a concomitant increase in p18(INK4C). Together, these findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate a bona fide tumor suppressor role for p18(INK4C) in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate proliferation.
Source: Cancer Cell
Authors: Ruprecht Wiedemeyer, Cameron Brennan, Timothy P. Heffernan, Yonghong Xiao, John Mahoney, Alexei Protopopov, Hongwu Zheng, Graham Bignell, Frank Furnari, Webster K. Cavenee, William C. Hahn, Koichi Ichimura, V. Peter Collins, Gerald C. Chu, Michael R. Stratton, Keith L. Ligon, P. Andrew Futreal, Lynda Chin
Institutions: Harvard University, Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, Wellcome Sanger Institute, University of California San Diego, Ludwig Cancer Research, Broad Institute, Brigham and Women's Hospital, University of Cambridge, Institute of Cancer Research
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
OpenAlex ID: W2123845663