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 language | English |
|---|---|
| Article number | 6870614 |
| Journal | Disease Markers |
| Volume | 2017 |
| DOIs | |
| Publication status | Published - Jan 1 2017 |
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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 journal › Article
}
TY - JOUR
T1 - Are Fusion Transcripts in Relapsed/Metastatic Head and Neck Cancer Patients Predictive of Response to Anti-EGFR Therapies?
AU - Bossi, Paolo
AU - Siano, Marco
AU - Bergamini, Cristiana
AU - Cossu Rocca, Maria
AU - Sponghini, Andrea P.
AU - Giannoccaro, Marco
AU - Tonella, Luca
AU - Paoli, Alessandro
AU - Marchesi, Edoardo
AU - Perrone, Federica
AU - Pilotti, Silvana
AU - Locati, Laura D.
AU - Canevari, Silvana
AU - Licitra, Lisa
AU - De Cecco, Loris
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85042216128&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042216128&partnerID=8YFLogxK
U2 - 10.1155/2017/6870614
DO - 10.1155/2017/6870614
M3 - Article
AN - SCOPUS:85042216128
VL - 2017
JO - Disease Markers
JF - Disease Markers
SN - 0278-0240
M1 - 6870614
ER -