[Genetics of laryngeal cancer: an experimental study]

Abstract

Squamous cell laryngeal carcinoma accounts for 1% of all cancer deaths and 95% of all laryngeal malignancies. It is most frequently found in smokers over 40 years of age. This neoplasm is presently the object of cytogenetic studies in an attempt to identify a specific chromosome pattern. In a study of 29 cases of malignant primary laryngeal tumor, Nawroz (1993) found a loss of alleles in different loci mapped in the short arm of chromosome 9 (9p) in more than two-thirds of the cases. In the same chromosome region, the loss of heterozygotes (LOH) was previously described in other neoplasms (leukemia, hematic tumors, melanomas). In an attempt to verify the predominant chromosome pattern and the loss of heterozygotes in chromosome 9, a cytogenetic, genetic-molecular study was performed on ten cases of laryngeal carcinoma. Among these subjects, two showed a hyperdiploid chromosome pattern (metaphase with more than 46 chromosomes per cell), five had a hypodiploid pattern (with less than 46 chromosomes per cell) while, for the remaining three cases, it was not possible to identify any metaphase. Numerous structural and numerical karyotype defects were found in chromosomes 1, 3, 4, 5, 9, 10, 13, 14, 16, 18, and Y. In 6 of the cases abnormality was found in chromosome 9 while in 10 it was apparently a homozygote. The study was performed with the use of fluorescent in situ hybridization (FISH) using a chromosome library specific for chromosome 9. A loss of the 9p segment could be found as a result of different types of alterations: deletion (case 1, 2, 5, 7); non uniform transfer between chromosome 2 and chromosome 9 (case 2); other transfers involving the 9p segment (case 1, 4, 5, 7, 10). In six cases, analysis was further detailed at the molecular level by means of DNA amplification methods (PCR) and electrophoresis on denatured 10% polyacrylammide gels. LOH was studied using a polymorphic system specific for the short arm of chromosome 9. Four of the cases examined showed LOH for the system used while one case (case 4) gave no information. Case 9 did not show any loss of alleles. The present study suggests that the loss of a DNA sequence on chromosome 9p is primary to the neoplastic progression in laryngeal cancer.