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

Paolo Bossi, Marco Siano, Cristiana Bergamini, Maria Cossu Rocca, Andrea P Sponghini, Marco Giannoccaro, Luca Tonella, Alessandro Paoli, Edoardo Marchesi, Federica Perrone, Silvana Pilotti, Laura D Locati, Silvana Canevari, Lisa Licitra, Loris De Cecco

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)6870614
JournalDisease Markers
Volume2017
DOIs
Publication statusPublished - 2017

Keywords

  • Journal Article

Fingerprint Dive into the research topics of 'Are Fusion Transcripts in Relapsed/Metastatic Head and Neck Cancer Patients Predictive of Response to Anti-EGFR Therapies?'. Together they form a unique fingerprint.

  • Cite this