Genetic model of transformation and neoplastic progression in laryngeal epithelium.

Abstract

The aim of this study was to analyze genetic alterations in the transformation-progression model of laryngeal tumors. Copy number changes of 37 genes were analyzed by multiple ligation-dependent probe amplification (MLPA) in 94 tissue samples. In the smoker normal mucosa group TP53 loss was predominant, whereas in the precursor lesions CDKN2A loss and CDKN2D gain were most frequent. Precursor lesions with progression presented CTNNB1 loss. In the carcinoma group the most common changes were CDKN2A, MLH1, CTNNB1, and CASP6 losses and RECQL4, CCND1, and EMS1 gains. Positive lymph node primary tumors were related to TP53, IL1A, and RB1 losses and STK11 gain. The lymph node metastases differed from their corresponding primary tumor in LMNA, RECQL4, and IGF1R losses, and N33 and CDKN2D gains. Genetic changes and new key genes were found to be associated with specific steps. We included new steps, not presented in the classic models: normal mucosa tobacco exposed, positive lymph node primary tumor, and corresponding lymph node metastases.