The Genomic Profiling in Chinese Head and Neck Cancer and Incidence of NTRK Fusion

Abstract

Background Head and neck cancers are aggressive epithelial tumors and well recognized as a particularly challenging class of tumors to treat. Comprehensive molecular profiling is leading to the development of “personalized” or “precision” medicine. Here we report the genomic profiling of Chinese head and neck cancers and the incidence of NTRK aberrations. Methods We retrospectively analyzed the genetic aberrations in 127 patients of Chinese head and neck cancer. All the patients were detected by 1021-gene panel (including NTRK1, NTRK2, NTRK3) of hybridization capture-based next-generation sequencing with tumor tissue and matched peripheral blood control samples. Results This studied was inspired by the outcome benefit of a parotid cancer patient harboring ETV6-NTRK3 fusion, who received crizotinib treatment and achieved a 2-year progression-free survival (PFS). Then, we reviewed 127 cases of head and neck cancer in our database. The most common histology type was HNSCC (79.5%). The genomic profiling indicated that both in our Chinese cohort and TCGA database, TP53 is the most frequently mutated gene in head and neck cancer. The incidence of NTRK genetic aberrations was 7.9% (10/127) including NTRK fusion (n = 4, 3.1%) and NTRK mutation (n = 6, 4.7%). The most common fusion was ETV6-NTRK3 (n = 3, 2.4%). Compared to NTRK-wt group, NTRK aberration group had more APC and PTPRD aberrations (p < 0.05). The association of genetic aberrations with tumor mutation burden (TMB) had been analyzed. NTRK fusion-group had a lower TMB compared to the NTRK-wt group (p = 0.034). TP53 and LRP1B showed significant association with higher TMB (both p < 0.01), which may be potential markers of immunotherapy in head and neck cancer patients. Conclusions Our data is the first study to report the genomic profiling in Chinese head and neck cancers and the incidence of NTRK fusion. About 3% of Chinese head and neck patients may benefit from targeted therapy of NTRK inhibitors. An ETV6-NTRK3 fusion patient reached a long-term response with crizotinib treatment,indicating crizotinib might be an alternative treatment option for patients with NTRK fusions.

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“…Moreover, ETV6-NTRK3 fusion was reported to be driver alteration triggering tumorigenesis of multiple cancer types, including secretory breast cancer, colorectal cancer and Spitz tumor [37,[45][46][47][48]. Recently, NTRK somatic mutations and ETV6-NTRK3 fusion were also reported in head and neck squamous cell cancers with a prevalence of 7.9% and 2.4% in Chinese patients (3/127; 10/127) respectively, and one of the ETV6-NTRK3 positive patient benefited from crizotinib treatment, offering an alternative treatment strategy [49]. Similar to CDKN2A, NTRK3 was observed recurrently mutated in our cohort, while no mutation was detected in CD cohort.…”