Are Fusion Transcripts in RelapsedMetastatic Head and Neck Cancer Patients Predictive of Response to Anti-EGFR Therapies?

Abstract EN

Prediction of benefit from combined chemotherapy and the antiepidermal growth factor receptor cetuximab is a not yet solved question in head and neck squamous cell carcinoma (HNSCC).

In a selected series of 14 long progression-free survival (PFS) and 26 short PFS patients by whole gene and microRNA expression analysis, we developed a model potentially predictive of cetuximab sensitivity.

To better decipher the “omics” profile of our patients, we detected transcript fusions by RNA-seq through a Pan-Cancer panel targeting 1385 cancer genes.

Twenty-seven different fusion transcripts, involving mRNA and long noncoding RNA (lncRNA), were identified.

The majority of fusions (81%) were intrachromosomal, and 24 patients (60%) harbor at least one of them.

The presence/absence of fusions and the presence of more than one fusion were not related to outcome, while the lncRNA-containing fusions resulted enriched in long PFS patients (P=0.0027).

The CD274-PDCD1LG2 fusion was present in 7/14 short PFS patients harboring fusions and was absent in long PFS patients (P=0.0188).

Among the short PFS patients, those harboring this fusion had the worst outcome (P=0.0172) and increased K-RAS activation (P=0.00147).

The associations between HNSCC patient’s outcome following cetuximab treatment and lncRNA-containing fusions or the CD274-PDCD1LG2 fusion deserve validation in prospective clinical trials.