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

Autor: Bossi P; Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Siano M; Department of Internal Medicine, Clinic for Medical Oncology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland., Bergamini C; Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Cossu Rocca M; Division of Medical Oncology, European Institute of Oncology, Milan, Italy., Sponghini AP; SC of Oncology, AOU Maggiore della Carità, Novara, Italy., Giannoccaro M; Functional Genomics and Bioinformatics, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Tonella L; Functional Genomics and Bioinformatics, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Paoli A; Functional Genomics and Bioinformatics, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Marchesi E; Functional Genomics and Bioinformatics, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Perrone F; Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Pilotti S; Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Locati LD; Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Canevari S; Functional Genomics and Bioinformatics, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Licitra L; Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; University of Milan, Milan, Italy., De Cecco L; Functional Genomics and Bioinformatics, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Jazyk: angličtina
Zdroj: Disease markers [Dis Markers] 2017; Vol. 2017, pp. 6870614. Date of Electronic Publication: 2017 Nov 12.
DOI: 10.1155/2017/6870614
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: