We study the genetic steps involved in the development of cancer. Two important genetic classes that regulate normal cell division are proto-oncogenes and tumor suppressor genes. Genetic lesions detected in a wide variety of cancers involve the loss or inactivation of tumor suppressor genes such as p53 on 17p or PTEN on 10q. We have used the PCR technique to screen different human cancers for alterations in a number of tumor suppressor genes (p16, p53, PTEN). Recently, we identified a new oncogene in B-cells from a patient with chronic lymphocytic leukemia which maps to 10p. Future studies require an assessment of its role in B-cell diseases.

Current studies focus on understanding the genetic basis of drug resistance and the genetic control of apoptosis. We follow changes in the expression of these genes (p53, p16, Rb, bcl-2/bax) in tissue culture models of drug-induced cell death. Failure to undergo cell death on the initiation of drug treatment may be one general mechanism for drug resistance. By assembling the total genetic picture of a given tumor from alterations in critical cancer-susceptibility genes (p53, bcl-2/bax), we may be able to develop better treatments for cancer.