Oncogene mutational profile in nasopharyngeal carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is a common tumor in Southern China, but the oncogene mutational status of NPC patients has not been clarified. Using time-of-flight mass spectrometry, 238 mutation hotspots in 19 oncogenes were examined in 123 NPC patients. The relationships between mutational status and clinical data were assessed with a χ(2) or Fisher's exact test. Survival analysis was performed using the Kaplan-Meier method with the log-rank test. In 123 patients, 21 (17.1%) NPC tumors were positive for mutations in eight oncogenes: six patients had PIK3CA mutations (4.9%), five NRAS mutations (4.1%), four KIT mutations (3.3%), two PDGFRA mutations (1.6%), two ABL mutations (1.6%), and one with simultaneous mutations in HRAS, EGFR, and BRAF (1%). Patients with mutations were more likely to relapse or develop metastasis than those with wild-type alleles (P=0.019). No differences or correlations were found in other clinical characteristics or in patient survival. No mutations were detected in oncogenes AKT1, AKT2, CDK, ERBB2, FGFR1, FGFR3, FLT3, JAK2, KRAS, MET, and RET. These results demonstrate an association between NPC and mutations in NRAS, KIT, PIK3CA, PDGFRA, and ABL, which are associated with patient relapse and metastasis.

Keywords: NPC; mutation; oncogene.

Figure 1

Representative graphs showing the mutations detected by time-of-flight mass spectrometry using NRAS-8. (A) Blank control. Only a peak representing the uncombined probe is apparent, with no sample peaks. (B) Negative control. A peak for the negative sample is shown, with no mutation peak or close chemical noise peak. However, there is a clear standard peak for the wild-type sample. (C) A typical mutation peak. The wild-type peak and a mutation peak are apparent, with no abnormality noted in the blank control (A) or negative control (B).

Figure 2

Kaplan–Meier survival curves for NPC patients. (A) Overall survival (OS) of the NPC patients with oncogene mutations vs that of wild-type patients. (B) Progression-free survival (PFS) of NPC patients with oncogene mutations vs that of wild-type patients.