Are Fusion Transcripts in Relapsed/Metastatic Head and Neck Cancer Patients Predictive of Response to Anti-EGFR Therapies?
| Title: | Are Fusion Transcripts in Relapsed/Metastatic Head and Neck Cancer Patients Predictive of Response to Anti-EGFR Therapies? |
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| Authors: | 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. |
| Source: | Disease markers [Dis Markers] 2017; Vol. 2017, pp. 6870614. Date of Electronic Publication: 2017 Nov 12. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Wiley Country of Publication: United States NLM ID: 8604127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1875-8630 (Electronic) Linking ISSN: 02780240 NLM ISO Abbreviation: Dis Markers Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2024 : [Hoboken, NJ] : Wiley; Original Publication: Chichester ; New York : Wiley, c1983-2024 |
| MeSH Terms: | Antineoplastic Agents, Immunological/*therapeutic use ; Biomarkers, Tumor/*genetics ; Carcinoma, Squamous Cell/*genetics ; Cetuximab/*therapeutic use ; Head and Neck Neoplasms/*genetics ; Oncogene Proteins, Fusion/*genetics; B7-H1 Antigen/genetics ; Carcinoma, Squamous Cell/drug therapy ; Carcinoma, Squamous Cell/metabolism ; ErbB Receptors/metabolism ; Head and Neck Neoplasms/drug therapy ; Head and Neck Neoplasms/metabolism ; Programmed Cell Death 1 Ligand 2 Protein/genetics ; Humans |
| 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. |
| References: | Oncogene. 2017 Jan 26;36(4):471-481. (PMID: 27345413); PLoS One. 2017 Jan 25;12 (1):e0170632. (PMID: 28122052); Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517); Urol Oncol. 2015 Sep;33(9):384.e9-20. (PMID: 26008593); PLoS One. 2010 Nov 15;5(11):e13984. (PMID: 21085593); Blood. 2014 Mar 27;123(13):2062-5. (PMID: 24497532); Clin Cancer Res. 2016 Aug 1;22(15):3961-70. (PMID: 26920888); Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18740-4. (PMID: 19841262); Curr Treat Options Oncol. 2017 May;18(5):32. (PMID: 28474265); Oncogene. 2015 Sep 10;34(37):4845-54. (PMID: 25500544); Leukemia. 2013 Nov;27(11):2165-76. (PMID: 23628958); Cancer Treat Rev. 2014 Feb;40(1):178-89. (PMID: 23993769); Cancer. 2008 Jan 1;112(1):94-103. (PMID: 18022917); Dis Markers. 2017;2017:7243968. (PMID: 28634418); Genome Biol. 2011 Aug 11;12(8):R72. (PMID: 21835007); Head Neck. 2008 Oct;30(10):1361-83. (PMID: 18642290); Nucleic Acids Res. 2016 Jun 2;44(10 ):4487-503. (PMID: 27105842); Ann Oncol. 2011 May;22(5):1078-87. (PMID: 21048039); J Clin Oncol. 2017 May 10;35(14 ):1542-1549. (PMID: 28328302); Eur J Cancer. 2013 Apr;49(6):1161-8. (PMID: 23265711); N Engl J Med. 2016 Nov 10;375(19):1856-1867. (PMID: 27718784); Nucleic Acids Res. 2013 Jan;41(Database issue):D246-51. (PMID: 23042674); Nat Rev Clin Oncol. 2015 Jan;12(1):11-26. (PMID: 25403939); Oncotarget. 2017 May 2;8(32):52889-52900. (PMID: 28881780); N Engl J Med. 2008 Sep 11;359(11):1116-27. (PMID: 18784101); Curr Oncol Rep. 2014 May;16(5):386. (PMID: 24623521); Cancer Inform. 2014 Jan 16;13:13-20. (PMID: 24526832); Oncotarget. 2016 Nov 8;7(45):74362-74379. (PMID: 27556186); Clin Cancer Res. 2017 Jun 15;23 (12 ):3158-3167. (PMID: 28619999); Genes (Basel). 2017 Jan 14;8(1):. (PMID: 28098823); Int J Cancer. 2016 Jul 15;139(2):373-82. (PMID: 26949921); Oncotarget. 2017 Jan 10;8(2):1972-1982. (PMID: 28030848); Cancer. 2004 Nov 15;101(10):2222-9. (PMID: 15452834) |
| Substance Nomenclature: | 0 (Antineoplastic Agents, Immunological); 0 (B7-H1 Antigen); 0 (Biomarkers, Tumor); 0 (CD274 protein, human); 0 (Oncogene Proteins, Fusion); 0 (PDCD1LG2 protein, human); 0 (Programmed Cell Death 1 Ligand 2 Protein); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (ErbB Receptors); PQX0D8J21J (Cetuximab) |
| Entry Date(s): | Date Created: 20171221 Date Completed: 20180803 Latest Revision: 20181202 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC5702394 |
| DOI: | 10.1155/2017/6870614 |
| PMID: | 29259349 |
| Database: | MEDLINE |
Journal Article