BACKGROUND: CUP management may be viewed as an epitome of personalised medicine as we apply our understanding of biological markers to this heterogeneous disease. There is a significant interest in evaluating actionable mutations in various signaling pathways, receptors and downstream effectors in CUP that may help us understand its biology and serve as the basis for unique targeted therapeutic approaches. Sequenom (SQM) Massarray platform enables rapid mutation profiling in solid tumors which we applied to CUP.
METHODS: 83 CUP samples were sent for DNA mass array analysis. Sequenom was run on 60 samples; 23 samples lacked sufficient quantity or quality of DNA. Data on clinicopathological features was collected.
RESULTS: Of the 60 patient samples run on SQM, 16 patients had changes including 11 mutations and 6 polymorphisms . The 6 polymorphisms were in MET . The mutations reported were :RAS (7; 6 KRAS, 1 NRAS), IDH1 (2), PI3K (1) and MET (1). Atleast 50% of the tumors were poorly differentiated. Interestingly, the 2 patients with IDH1 mutations presented with osseous predominant metastatic disease. Of the 6 patients with KRAS mutations, 4 presented with a gastrointestinal profile ( CDX2+ or CK20+) on IHC; in all 4, the DNA sequencing analysis results matched the sequenom results.
CONCLUSIONS: The (all-comers) overall mutation rate in a heterogenous CUP population is low (11/60, 18%). No "new" low frequency mutations were found using the current panel (Table). Rare and potentially targetable mutations may be identified with a larger panel. Focusing on CUP subsets using this approach may also provide a higher mutational yield.
