Loss of heterozygosity in squamous cell carcinomas of the head and neck defines a tumor suppressor gene region on 11q13.
Tumor suppressor genes APC, RB1, and DCC, as well as genes localized to 3p and 11q, have been implicated in the development of a number of human tumors. To determine whether allelic deletions occur at these loci in squamous cell carcinomas (SSCs) of the head and neck, 25 primary, 1 metastatic, and 3 recurrent tumors, along with the corresponding constitutional tissues, were analyzed by using a battery of polymorphic DNA markers. For two primary tumors, we also analyzed subsequent metastatic tumors of the lung. Polymerase chain reaction-based restriction fragment length polymorphism studies demonstrated loss of heterozygosity for the APC gene in 2 of 12 (17%), the RB1 gene in 5 of 22 (23%), and the DCC gene in 5 of 13 (38%) informative cases. Alleles on chromosomes 3p, 11q13, and 18q21.1 were lost in 7 of 20 (35%), 9 of 23 (39%), and 4 of 17 (24%) informative cases, respectively. A breakpoint was identified within the chromosomal region 3p13-21.2 in a SCC of the tongue. Breakpoints within 11q13 were identified in 2 additional tumors. Thus, allelic deletions of DCC, 3p, and 11q13 appear to be common in head and neck cancers, suggesting that these genes play a critical and complex role in the development of these tumors. Furthermore, the present study provides definitive evidence for a tumor suppressor gene at chromosome band 11q13 and localizes this gene to the INT2-D11S533 interval for future cloning and sequencing.
VA Medical Center, Department of Surgery, UCLA School of Medicine 90073, USA.
M
M
Venugopalan
T F
TF
Wood
S P
SP
Wilczynski
S
S
Sen
J
J
Peters
G C
GC
Ma
G A
GA
Evans
E S
ES
Srivatsan
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016160:Retinoblastoma Protein / Q000235:genetics; D017384:Sequence Deletion
D016160:Retinoblastoma Protein