Characterization of tumor-specific DNA sequences: molecular grading of the astrocytomas.

Abstract

Tumor-specific DNA sequences or unique sequences have been found in a number of human cancer cells including gliomas but not in equivalent normal cells. In a continuing effort to further elucidate the nature of these sequences, thermal analysis using the hydroxyapatite technique was carried out on the various grades of astrocytomas. A recycled DNA molecular probe from Grade IV astrocytomas was annealed to the various grades of astrocytoma DNAs and to normal brain DNA which served as control. There was an increasing percentage of hybridization in direct proportion to the degree of malignancy. The same results were obtained using a recycled DNA probe from medulloblastomas. Thermal melt analysis of these same tumors revealed a Tm (melting temperature or temperature of reassociation) of about 83 degrees C, irrespective of degree or grade of malignancy. These results would indicate that the type of genetic DNA sequences or tumor-specific DNA sequences involved in this type of tumor is the same, whether the tumor is benign or malignant. The demonstration of the increasing percentage of hybridization based on the increasing degree or grade of malignancy and the further demonstration that the involved tumor-specific DNA sequences are the same irrespective of the degree of malignancy, justify the conclusion that the number of copies of these sequences determines the degree or grade of malignancy. Pending further laboratory confirmation, this fact may be assumed to be true with respect to cancers from other organ sites.