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

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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
Article number6870614
JournalDisease Markers
Volume2017
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Head and Neck Neoplasms
Fusion reactions
Disease-Free Survival
Long Noncoding RNA
Therapeutics
Growth Factor Receptors
Neoplasm Genes
Genes
MicroRNAs
Chemotherapy
Ports and harbors
Clinical Trials
RNA
Gene Expression
Drug Therapy
Messenger RNA
Chemical activation
Cetuximab
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Are Fusion Transcripts in Relapsed/Metastatic Head and Neck Cancer Patients Predictive of Response to Anti-EGFR Therapies? / Bossi, Paolo; Siano, Marco; Bergamini, Cristiana; Cossu Rocca, Maria; Sponghini, Andrea P.; Giannoccaro, Marco; Tonella, Luca; Paoli, Alessandro; Marchesi, Edoardo; Perrone, Federica; Pilotti, Silvana; Locati, Laura D.; Canevari, Silvana; Licitra, Lisa; De Cecco, Loris.

In: Disease Markers, Vol. 2017, 6870614, 01.01.2017.

Research output: Contribution to journalArticle

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AU - Sponghini, Andrea P.

AU - Giannoccaro, Marco

AU - Tonella, Luca

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AU - Marchesi, Edoardo

AU - Perrone, Federica

AU - Pilotti, Silvana

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AU - De Cecco, Loris

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