IDENTIFICATION OF PRIMARY CHROMOSOME-ABNORMALITIES IN A PATIENT WITH ENDOMETRIAL CARCINOMA - ANALYSES OF TUMOR-BIOPSY AND LYMPHOCYTE-CULTURES

The development of human cancer is generally considered to be the resu lt of genetic mutations that cause a progressively more malignant phen otype. We propose that such genetic changes can be observed in a small number of lymphocytic metaphase plates. We have identified a specific chromosome marker formation in a primary endometrial adenocarcinoma o btained from a 74-year-old woman. After observing an isochromosome for 1q in the tumor cells, we predicted that in her lymphocytes this part icular chromosome must show susceptibility to breakage. After 6 months , when lymphocytes were available from this patient, 4.0% of her metap hases exhibited chromatid breaks in the pericentromeric region of one homolog of chromosome 1, thus confirming our prediction. Since then, t he primary endometrial tumor cell line has been passaged through nude mice and has become highly metastatic. Examination of tumors obtained from different organ sites of these mice has revealed that the same al tered homolog 1 underwent various types of chromosome and chromatid ab errations, thereby confirming the presence of instability in this part icular chromosome in this particular cancer. A detailed karyotypic evo lution from normal lymphocyte cultures --> primary endometrial tumor - -> highly metastatic endometrial tumor was therefore possible to const ruct. Our results further support the idea that peripheral blood lymph ocytes can be used as the tissue for studying genetics of cancer predi sposition.