The molecular landscape of recurrent and metastatic head and neck cancers insights from a precision oncology sequencing platform Journal Article
| Authors: | Morris, L. G. T.; Chandramohan, R.; West, L.; Zehir, A.; Chakravarty, D.; Pfister, D. G.; Wong, R. J.; Lee, N. Y.; Sherman, E. J.; Baxi, S. S.; Ganly, I.; Singh, B.; Shah, J. P.; Shaha, A. R.; Boyle, J. O.; Patel, S. G.; Roman, B. R.; Barker, C. A.; McBride, S. M.; Chan, T. A.; Dogan, S.; Hyman, D. M.; Berger, M. F.; Solit, D. B.; Riaz, N.; Ho, A. L. |
| Article Title: | The molecular landscape of recurrent and metastatic head and neck cancers insights from a precision oncology sequencing platform |
| Abstract: | IMPORTANCE Recurrent and/or metastatic head and neck cancer is usually incurable. Implementation of precision oncology for these patients has been limited by incomplete understanding of the molecular alterations underlying advanced disease. At the same time, the molecular profiles of many rare head and neck cancer types are unknown. These significant gaps in knowledge need to be addressed to rationally devise new therapies. OBJECTIVE To illuminate the distinct biology of recurrent and metastatic head and neck cancers and review implementation of precision oncology for patients with advanced disease. DESIGN, SETTING, AND PARTICIPANTS After exclusions, 151 patients with advanced, treatment-resistant head and neck tumors, including squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), and other salivary and cutaneous cancers, whose tumorswere sequenced between January 2014 and July 2015 at Memorial Sloan Ketteringwere recruited. Next-generation sequencing of tumors as part of clinical care included high-depth (median 600×) exonic coverage of 410 cancer genes and whole-genome copy number analysis. INTERVENTIONS Next-generation sequencing of tumors and matched normal DNA. MAIN OUTCOMES AND MEASURES Feasibility, the frequency of actionable molecular alterations, the effect on decision making, and identification of alterations associated with recurrent and metastatic disease. RESULTS Overall, 151 patients (95menand 56women mean [range] age, 61.8 [17-100] years) were included in the study. Next-generation sequencing ultimately guided therapy in 21 of 151 patients (14%) (13 of 53 [25%]of patients with HNSCC) by refining diagnoses and matching patients to specific therapies, in some cases with dramatic responses on basket studies. Molecular alterationswere potentially actionable in 28 of 135 patients (21%). The genetic profiles of recurrent andmetastatic tumorswere often distinct from primary tumors. Compared to primary human papillomavirus (HPV) -positive tumors, many recurrent andmetastaticHPVpositive tumors exhibited a molecular profile more similar toHPV-negative tumors, including enriched frequencies of TP53 mutation (3 of 20tumors [15%]), whole genome duplication (5 of 20tumors [25%]), and 3p deletion (11 of 20tumors [55%]). Therewere high rates of TERT promoter mutation in recurrent andmetastaticHPV-negative HNSCC (13 of 30 tumors [43%]), cutaneous SCC (11 of 21 tumors [52%]), basal cell carcinoma (3 of 4 tumors [75%]), andACC (5 of 36 tumors [14%]). ActivatingNOTCH1 mutationswere enriched inmetastaticACCs (8 of 36 tumors [22%]). CONCLUSIONS AND RELEVANCE These findings reveal the molecular landscape of advanced disease and rare cancer subtypes, both predominant challenges in head and neck oncology. To understand the repertoire of targetable alterations in advanced cancers, it is necessary to sequence recurrent and metastatic tumors. These data are important first steps toward implementation of precision head and neck oncology. Copyright 2016 American Medical Association. All rights reserved. |
| Journal Title: | JAMA Oncology |
| Volume: | 3 |
| Issue: | 2 |
| ISSN: | 2374-2437 |
| Publisher: | American Medical Association |
| Date Published: | 2017-02-01 |
| Start Page: | 244 |
| End Page: | 255 |
| Language: | English |
| DOI: | 10.1001/jamaoncol.2016.1790 |
| PROVIDER: | scopus |
| PMCID: | PMC5253129 |
| PUBMED: | 27442865 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 June 2017 -- Source: Scopus |
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