Genetic Characteristics of Recurrent and Metastatic Head and Neck Cancers
By Matthew Stenger Posted: 8/4/2016 10:24:59 AM Last Updated: 8/4/2016 10:24:59 AM Tweet this page
In patients with advanced treatment–resistant head and neck tumors, potentially actionable alterations were found in 21% with identified alterations.
TERT promoter mutations were found in many HPV-negative tumors.
Next-generation sequencing of recurrent or metastatic head and neck tumors at Memorial Sloan Kettering Cancer Center (MSK) has provided insight into the molecular characteristics of these tumors, which may aid in the implementation of precision treatment. Morris et al reported these findings in JAMA Oncology.
The study included 151 patients with advanced treatment–resistant head and neck tumors, including squamous cell carcinoma (HNSCC), adenoid cystic carcinoma, and other salivary and cutaneous cancers. Tumors were sequenced between January 2014 and July 2015 at MSK. Next-generation sequencing included high-depth exonic coverage of 410 cancer genes and whole-genome copy number analysis.
Sequencing results guided therapy in 21 patients (14%), including 13 of 53 (25%) with HNSCC, by refining diagnosis and matching patients to specific treatments; in some cases, dramatic responses were achieved in basket studies, according to the investigators. Among 135 patients with tumors with molecular alterations, alterations were potentially actionable in 28 patients (21%).
Molecular profiles of recurrent/metastatic tumors frequently differed from those of primary tumors. Compared with primary human papillomavirus (HPV)-positive tumors, many of the 20 recurrent/metastatic HPV-positive tumors exhibited a profile more closely resembling HPV-negative tumors, including higher frequency of TP53 mutation (3 tumors, 15%), whole-genome duplication (5 tumors, 25%), and 3p deletion (11 tumors, 55%). Among HPV-negative tumors, TERT promoter mutations were found in 13 of 30 (43%) HNSCCs, 11 of 21 (52%) cutaneous squamous cell carcinomas, 3 of 4 (75%) basal cell carcinomas, and 5 of 36 (14%) adenoid cystic carcinomas. Metastatic adenoid cystic carcinomas were enriched for activating NOTCH1 mutations in 8 of 36 cases (22%).
The investigators concluded: “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.”
The study was supported by the National Institutes of Health, Damon Runyon Cancer Research Foundation, and Society of Memorial Sloan Kettering Cancer Center.
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