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 result of genetic mutations that cause a progressively more malignant phenotype. We propose that such genetic changes can be observed in a small number of Iymphocytic metaphase plates. We have identified a specific chromosome marker formation in a primary endometrial adenocarcinoma obtained from a 74-year-old woman. After observing an isochromosome for 1q in the tumor cells, we predicted that in her lymphocytes this particular chromosome must show susceptibility to breakage. After 6 months, when lymphocytes were available from this patient, 4.0% of her metaphases exhibited chromatid breaks in the pericentromeric region of one homolog of chromosome 1, thus confirming our prediction. Since then, the 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 altered homolog 1 underwent various types of chromosome and chromatid aberrations, thereby confirming the presence of instability in this particular chromosome in this particular cancer. A detailed karyotypic evolution from normal lymphocyte cultures → primary endometrial tumor → highly metastatic endometrial tumor was therefore possible to construct. Our results further support the idea that peripheral blood lymphocytes can be used as the tissue for studying genetics of cancer predisposition.