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

Inga Marie Schaefer, Yuexiang Wang, Cher Wei Liang, Nacef Bahri, Anna Quattrone, Leona Doyle, Adrian Marinõ-Enríquez, Alexandra Lauria, Meijun Zhu, Maria Debiec-Rychter, Susanne Grunewald, Jaclyn F. Hechtman, Armelle Dufresne, Cristina R. Antonescu, Carol Beadling, Ewa T. Sicinska, Matt Van De Rijn, George D. Demetri, Marc Ladanyi, Christopher L. CorlessMichael C. Heinrich, Chandrajit P. Raut, Sebastian Bauer, Jonathan A. Fletcher

Research output: Contribution to journalArticle

18 Scopus citations


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.

Original languageEnglish (US)
Article number14674
JournalNature communications
StatePublished - Mar 8 2017


ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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., ... Fletcher, J. A. (2017). MAX inactivation is an early event in GIST development that regulates p16 and cell proliferation. Nature communications, 8, [14674].