In a pre-print electronic publication of the July 7, 2016 edition of Clinical Cancer Research, a team of Italian researchers examined the link between “Quadruple-Negative” GISTs (those that do not exhibit KIT, PDGFRA, or BRAF mutations as well as SDH gene inactivation) and Neurofibromatosis 1 (NF1) so as to better understand the molecular drivers of Quadruple-Negative GIST. The authors estimate that Quadruple-Negative GISTs may represent about 10% of all GISTs, and also note that they are poorly responsive to standard treatments.

Molecular profiling was done on 22 Quadruple-Negative GISTs with no prior diagnosis of NF1, and for comparison, 24 GISTs that had either KIT or PDGFRA mutations or SDH gene mutations were also analyzed. Most of the Quadruple-Negative patients had an intestinal tumor location and were female.

Results of Study

Results showed that 13 of the 22 Quadruple-Negative GIST tumors (59.1%) tested positive for NF1 as well. The authors noted that the presence of multifocal tumors and a multinodular pattern of growth were also common findings for those Quadruple-Negative tumors that also had NF1 mutations present.

Per the authors, these findings have clinical implications for Quadruple-Negative GIST patients. As there is potential for the presence of NF1 mutations as well, Quadruple-Negative GIST patients should also be tested for NF1 mutations, especially if their tumor is multifocal or with a multinodular growth pattern and is in a location other than the stomach.

Please note that this abstract can be accessed via PubMed by clicking this link:

We will be watching for further studies as they are published to determine the repercussions for potential treatment options.