Gastrointestinal stromal tumors are mesenchymal tumors which predominantly originate from the interstitial cells of Cajal in the intestinal lining. Around ~85% of malignant GISTs possess activating mutations in the tyrosine kinase receptors KIT or PDGFRA. The driver mutations in genes other than KIT or PDGFRA account for around 15% GISTs and belong to highly heterogeneous groups called wild-type GISTs. Around 20–40% of WT-GISTS are deficient for the succinate dehydrogenase complex (SDHA, SDHB, SDHC, SDHD). 

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors that occur in many organs. The routinely used IHC markers for NEN diagnosis include chromogranin A (CgA), synaptophysin, Ki67 and CD56. These markers have limitations including a lack of correlation to clinical outcomes and their presence in non-tumor tissue. Identification of additional markers in NEN tissue has the potential to improve clinical outcomes. We generated a detailed tumor profile of tissue from a patient with a grade 3 colonic NEC using phenotypic cancer markers and correlated this with the marker expression of the corresponding patient circulating tumor cells.

MPNSTs are aggressive Schwann cell-derived sarcomas, frequently associated with NF1 mutations. Traditional treatments, including surgery and chemotherapy, are largely ineffective, highlighting the urgent need for novel therapeutic strategies. NF1 loss leads to RAS pathway activation, which in turn activates multiple signaling cascades, including RAF-MEK-ERK1/2, PI3K-AKT, and RalGDS pathways. Inhibition of these pathways has been explored, with MEK inhibitors, such as selumetinib, showing some promise in clinical trials (NCT03433183).