1.Dept clinical Genetics, University Hospital, SE-221 85 Lund, Sweden
Fluorescence in situ hybridization (FISH) FISH analysis has recently been undertaken to verify and in detail characterize the most common recurrent chromosomal changes in head and neck SCC (HNSCC), including laryngeal SCC. FISH has demonstrated that cytogenetically detectable hsr in these tumors almost always corresponds to amplification of DNA sequences originating from 11q13, and the amplicons mapped vary in size from 3.5 to 4.5 Mb with a core of 1.5 - 1.7 Mb, and often many oncogenes in this region are coamplified, including CCND1, FGF3, FGF4, EMS1, and SHANK2. Another finding is that the amplification of 11q13 is often concomitant with deletion of distal 11q. The latter finding indicates that not only the amplification of one or more dominantly acting oncogenes in 11q13, but also loss of a tumor suppressor gene in the distal part of 11q, are critical for the development of laryngeal SCC. Detailed FISH characterization of pericentromeric rearrangements, in particular for chromosomes 1 and 8, with the use of YAC clones spanning the pericentromeric region of chromosomes, suggest that the essential outcome of these rearrangements at DNA level is the resulting genomic imbalances, i.e., loss or gain of neoplasia-associated genes. Furthermore, more precise mapping of breakpoints on chromosomal arms 1p and 8p has delineated critical regions for deletions within 1p11-p13 and the subtelomeric region of 8p.
Genetic imbalances revealed by CGH, allelotyping, and LOH studies A large scale effort has been devoted to the identification of tumor suppressor gene loci and amplified oncogenes in laryngeal carcinomas. Earlier loss of heterozygosity (LOH) studies focused on specific chromosomal arms pointed out the frequent loss of alleles from 3p, 8p, 9p, 13q and 17p in head and neck SCC (HNSCC) in general as well as in laryngeal SCC.A number of recent studies based on allelotyping or comparative genomic hybridization (CGH) indicate that HNSCC, including laryngeal SCC, display massive and widespread genomic imbalances and that certain chromosome segments are lost more often than others. Combined data in these studies indicate that the most frequent imbalances is loss of genetic material from 3p, 8 p, 9p, 13q, and 17p, found in more than 50% of the cases and less frequently, deletions in 3q, 4p, 4q, 6p, 6q, 8p, 8q, 11q, 14q, 17q, 19q, and 20p observed in 30-50% of the cases. Overrepresentation of genetic material occurs often in chromosomal arms 3q, 7p, 8q, 9q, and in chromosomal band 11q13.
Charlotte Jin ; Yuesheng Jin
Head and Neck: Laryngeal squamous cell carcinoma
Atlas Genet Cytogenet Oncol Haematol. 2006-09-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/5367/larynsquamcellid5367