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Loss of Heterozygosity Involves Multiple Tumor Suppressor Genes in Human Esophageal Cancers¹

Departments of Microbiology and Immunology [Y. H.], Medicine (Gastroenterology Division) [R. F. B., R. J. S., J. Y., Y. T., S. J. M.], Pathology [C. N., J. H. R., S. J. M.], Cancer Center [R. S., S. J. M.], and Molecular and Cell Biology Graduate Program [T. K. M., S. J. M.], University of Maryland and Baltimore Veterans Affairs Hospitals, Baltimore, Maryland 21201 and Department of Medicine (GI Division), University of Washington, Seattle, Washington 98195 [P. L. B., B. J. R.]

² To whom requests for reprints should be addressed, at Medicine/GI, University of Maryland, Room N3W62, 22 S. Greene St., Baltimore, MD 21201.

Loss of heterozygosity occurring on various chromosomes has been described in the majority of human tumors. The targets of frequent or consistent subchromosomal deletions are believed to be tumor suppressor genes. We examined 72 esophageal tumors (46 squamous cell carcinomas and 26 adenocarcinomas) for loss of heterozygosity at the p53, Rb, APC, MCC, and DCC loci. Inclusion of these tumor suppressor genes in the allelic deletions was directly ascertained by performing polymerase chain reaction at polymorphic sites within the genes. Loss of heterozygosity occurred in 55% of informative cases at p53, in 48% of informative cases at Rb, in 66% at APC, in 63% at MCC, and in 24% at DCC. Ninety-three % of tumors informative at all loci (fully informative) lost heterozygosity of at least one locus. A high percentage of fully informative tumors (71%) also lost heterozygosity at more than one locus. There were no significant differences among histological types in the prevalence of loss of heterozygosity at any locus. There were correlations of losses involving MCC versus DCC, Rb, and p53. These data suggest that (a) allelic deletions including these tumor suppressor genes are important in the formation and/or progression of most esophageal cancers; (b) allelic deletions involving MCC may not occur independently of deletions involving other tumor suppressor genes; and (c) the accumulation of multiple allelic deletions involving specific tumor suppressor genes may be important in most esophageal tumorigenesis or tumor evolution.

¹ This work was supported by grants from the Department of Veterans Affairs, the American Cancer Society (PDT-419 and PDT-316), the Ryan Hill Research Foundation, the Crohn's and Colitis Foundation of America, the Frank C. Bressler Research Fund, and SRIS/GRA support from the University of Maryland.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 5/11/92. Accepted 9/23/92.

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