Loss of heterozygosity in squamous cell carcinomas of the head and neck defines a tumor suppressor gene region on 11q13.

Abstract 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.