MAX inactivation is an early event in GIST development that regulates p16 and cell proliferation Journal Article


Authors: Schaefer, I. M.; Wang, Y.; Liang, C. W.; Bahri, N.; Quattrone, A.; Doyle, L.; Marinõ-Enríquez, A.; Lauria, A.; Zhu, M.; Debiec-Rychter, M.; Grunewald, S.; Hechtman, J. F.; Dufresne, A.; Antonescu, C. R.; Beadling, C.; Sicinska, E. T.; Van De Rijn, M.; Demetri, G. D.; Ladanyi, M.; Corless, C. L.; Heinrich, M. C.; Raut, C. P.; Bauer, S.; Fletcher, J. A.
Article Title: MAX inactivation is an early event in GIST development that regulates p16 and cell proliferation
Abstract: KIT, PDGFRA, NF1 and SDH mutations are alternate initiating events, fostering hyperplasia in gastrointestinal stromal tumours (GISTs), and additional genetic alterations are required for progression to malignancy. The most frequent secondary alteration, demonstrated in ∼70% of GISTs, is chromosome 14q deletion. Here we report hemizygous or homozygous inactivating mutations of the chromosome 14q MAX gene in 16 of 76 GISTs (21%). We find MAX mutations in 17% and 50% of sporadic and NF1-syndromic GISTs, respectively, and we find loss of MAX protein expression in 48% and 90% of sporadic and NF1-syndromic GISTs, respectively, and in three of eight micro-GISTs, which are early GISTs. MAX genomic inactivation is associated with p16 silencing in the absence of p16 coding sequence deletion and MAX induction restores p16 expression and inhibits GIST proliferation. Hence, MAX inactivation is a common event in GIST progression, fostering cell cycle activity in early GISTs. © 2017 The Author(s).
Journal Title: Nature Communications
Volume: 8
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2017-03-08
Start Page: 14674
Language: English
DOI: 10.1038/ncomms14674
PROVIDER: scopus
PMCID: PMC5344969
PUBMED: 28270683
DOI/URL:
Notes: Article -- Export Date: 3 April 2017 -- Source: Scopus
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  1. Cristina R Antonescu
    897 Antonescu
  2. Marc Ladanyi
    1328 Ladanyi
  3. Jaclyn Frances Hechtman
    212 Hechtman