EXPRESSION OF ABDB-TYPE HOMEOBOX GENES IN HUMAN TUMORS

BACKGROUND: Homeobox (HOX) genes of the ANT-C/BX-C type control rostra l-caudal patterning during embryogenesis. Previous work has shown that tissues express unique HOX gene expression profiles that persist upon transplantation to distant sites. These properties suggest that analy sis of HOX genes may be useful for the diagnosis and evaluation of pri mary and metastatic tumors. EXPERIMENTAL DESIGN: We analyzed normal an d neoplastic tissues for the expression of three AbdB-type HOX genes; HOXD10, HOXA9, and HOXC9 to evaluate three hypotheses: (a) that tumors express HOX genes found in their tissue of origin, (b) that metastati c tumors continue to express HOX genes found in the primary tumor, and (c) that the level of HOX expression is related to tumor grade. RESUL TS: Malignant tumors gave consistent patterns of HOX gene expression t hat paralleled their tissues of origin. Normal kidney and Wilm's tumor s expressed all three genes. Other renal tumors expressed distinct per mutations of the three genes. One epithelial Wilm's tumor expressed on ly an aberrant 0.3 kb HOXD10 transcript. Outside of the kidney, HOXD 1 0 was most characteristic of uterine tumors, HOXA9 of colonic adenocar cinomas, and HOXC9 of two groups of tumors: neoplasms derived from neu ral crest and mesenchymal tumors derived from intermediate mesoderm. M etastatic tumors retained their HOX gene expression profiles and did n ot express HOX genes transcribed at the site of metastasis. While modu lation of HOX gene expression was observed in some poorly differentiat ed tumors this was not a consistent measure of tumor grade. CONCLUSION S: HOX gene profile was a reliable indicator of histologic subtype in a variety of tumors and in selected cases provided useful diagnostic i nformation. Persistent expression in metastatic tumors confirmed that HOX expression profiles are potentially useful for diagnosing tumors o f unknown origin. Continued analysis of the relationship between level of expression and tumor grade/behavior is indicated.