Cytogenetics of epithelial malignant lesions

Chromosomal abnormalities have been believed to be responsible for neoplastic transformation and tumor growth for a long time. The confirming observations are of two types: (1) primary cytogenetic alterations that are responsible for tumor initiation and (2) secondary abnormalities that are acquired late and are associated with tumor growth, heterogeneity, and metastasis. Primary chromosomal abnormalities (such as the 13q deletion in retinoblastoma, 11p deletion in Wilms' tumor, 3p anomalies in renal cell carcinoma, and 5q deletion in colorectal carcinomas) first were identified in lymphocyte cultures as constitutional defects. Later, similar types of defects were observed as tumor-specific aberrations from patients whose lymphocytes otherwise had normal chromosomes. Recently, it has become clear that classes of known cancer-related genes (dominant protooncogenes and recessive tumor-suppressor or anti-oncogenes) are located at those hot spots that are involved in neoplasia-associated chromosomal alterations. In breast carcinoma, such a specific chromosomal alteration has not been identified conclusively in lymphocyte cultures, although chromosome 1 alterations have been observed in cell lines, directly processed effusions, and primary breast tumors. Lymphocyte cultures; primary tumors; and established cell lines from breast carcinomas, colorectal carcinomas, and renal cell carcinomas were analyzed to identify (1) primary chromosomal alterations precisely and (2) secondary cytogenetic defects that are associated with these most common solid adult neoplasms. Peripheral blood analysis indicated that chromosomes 1, 17, and 18 in breast carcinomas; chromosomes 3 and 14 in renal cell carcinomas; and chromosomes 5, 12, and 17 in colorectal carcinomas were involved nonrandomly in structural anomalies in a small number of lymphocyte cells (1-4%). These chromosomal aberrations were considered primary defects because of their involvement as marker formations in tumor cells; other structural and numeric abnormalities also were found. These results indicate that lymphocyte chromosomal analysis might identify those at high risk for breast, colorectal, and renal cell carcinomas, among other malignant lesions. Such identifications could facilitate early selection for primary and secondary cancer prevention or interventional trials.