Genetic model of transformation and neoplastic progression in laryngeal epithelium.
BACKGROUND
The aim of this study was to analyze genetic alterations in the transformation-progression model of laryngeal tumors.


METHODS
Copy number changes of 37 genes were analyzed by multiple ligation-dependent probe amplification (MLPA) in 94 tissue samples.


RESULTS
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.


CONCLUSIONS
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.
Marcos
César Álvarez
CÁ
Department of Otorhinolaryngology, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
Alonso-Guervós
Marta
M
Prado
Nuria Rodríguez
NR
Gimeno
Teresa Sampedro
TS
Iglesias
Francisco Domínguez
FD
Hermsen
Mario
M
Llorente
José Luis
JL
D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D006801:Humans; D007820:Laryngeal Mucosa / Q000473:pathology*; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology*; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology*; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013030:Spain