Genetic model of transformation and neoplastic progression in laryngeal epithelium

Abstract

Background: To analyse genetic alterations in the transformation-progression model of larynx tumors. Methods: Copy number changes of 37 genes were analyzed by MLPA in 94 tissue samples. Results: In the smoker normal mucosa group TP53 loss was predominant, while 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, CASP6 losses and RECQL4, CCND1, EMS1 gains. Positive lymph node primary tumors were related to TP53, IL1A, RB1 losses and STK11 gain. The lymph node metastases differed from their corresponding primary tumor in LMNA, RECQL4 and IGF1R losses, and N33, CDKN2D gains. Conclusions: Genetic changes and new key genes were found associated to specific steps of transformation-progression. We included new steps, not presented in the classical models: normal mucosa tobacco exposed, positive lymph node primary tumor and corresponding lymph node mestatases.