The mutational spectrum of squamous-cell carcinoma of the head and neck: targetable genetic events and clinical impact.
Squamous-cell cancer of the head and neck (SCCHN) represents a heterogeneous disease entity, with various etiological factors implicated in the genesis of distinct molecular subsets of tumors, which exhibit different biological and clinical behavior. Treatment of SCCHN is expected to change in the next decade as targeted therapies continue to make strides. Recently, next-generation sequencing studies conducted on ∼190 SCCHN specimens shed light into the molecular pathogenesis of the disease. These studies discovered mutations in genes involved in the differentiation program of squamous epithelium and the Notch/p63 axis (such as NOTCH1, TP63 and FBXW7), and validated genetic alterations derived from previous studies (such as mutations in TP53, CDKN2A, PIK3CA, CCND1 and HRAS) as driver genetic events in SCCHN neoplastic transformation. More recently, comprehensive data from The Cancer Genome Atlas (TCGA) project on 306 SCCHN specimens provided further insight into SCCHN inherent molecular complexity, identifying novel significantly mutated genes, including FAT1, MLL2, TGFRBR2, HLA-A, NFE2l2 and CASP8. In this article, we provide an overview of the mutational spectrum of SCCHN, with emphasis on the clinical implementation of this knowledge. We also discuss the potential integration of new data within the framework of precision cancer medicine.
Department of Medical Oncology, University of Athens School of Medicine, Athens, Greece.
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Mountzios
Department of Surgery, Section of Otolaryngology, Yale University School of Medicine, New Haven,USA.
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Rampias
Second Department of Internal Medicine, Section of Medical Oncology, Attikon University Hospital, Athens, Greece; Department of Medicine, Yale Cancer Center, Yale University School of Medicine, New Haven,USA. Electronic address: diamando.psyrri@yale.edu.
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Psyrri
D063646:Carcinogenesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D057089:Pathology, Molecular; D017422:Sequence Analysis, DNA; D000077195:Squamous Cell Carcinoma of Head and Neck
D009363:Neoplasm Proteins
SCCHN; deep sequencing; genetic aberrations; somatic mutations