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Genetic events specific to the pathogenesis of malignancy can offer clues to the tumorigenesis process. The objective of this study was to identify gene alterations that differentiate tumor and nontumor lesions in squamous head and neck cancer (HNSCC). DNA from 220 primary HNSCC with concurrently present tumor and nontumor lesions from the same patient was interrogated for genomic alterations of loss or gain of copy. Conditional logistic regression dealt with tumor and non-tumor records within a patient. Of 113 genes, 53 had univariate effects ( P  < 0.01), of which 16 genes remained in the multivariable model with  P  < 0.01. The model had a C-index (ROC) of 0.93. Loss of  CDKN2B  and gain of  BCL6, FGF3 , and  PTP4A3  predicted tumor. Loss of  BAK1  and  CCND1  and gain of  STCH  predicted nontumor. This highly powered model assigned alterations in 16 genes specific for malignant versus nonmalignant lesions, supporting their contribution to the pathogenesis of HNSCC as well as their potential utility as relevant targets for further evaluation as markers of early detection and progression.

Malignant and Nonmalignant Gene Signatures in Squamous Head and Neck Cancer