HBUB1 defects in leukemia and lymphoma cells.

Abstract

Tumorigenesis is a multi-step process involving a series of changes of cellular genes. Most solid tumors and hematopoietic malignancies often show abnormal chromosome numbers, the aneuploidy. The chromosomal aneuploidy keeps cells in the state of chromosomal instability (CIN) that will increase the mutation rate of cells affected and thus push them deeper into the process of tumorigenesis. The yeast genetic studies showed that normal distribution of chromosome during mitosis is under the surveillance of a set of genes, the spindle assembly checkpoint genes, that include the BUB and MAD gene groups and MPS. In some colorectal cancers with CIN it was found to have hBUB1 gene mutated and the mutated gene functions dominantly. We have examined a series of breast cancer cell lines with or without CIN for the hBUB1 gene mutation and found none. However, we detected various degrees of deletion in the coding sequences of the hBUB1 gene in cells from T lymphoblastic leukemia cell lines, Molt3 and Molt4, and cells from some acute lymphoblastic leukemia and Hodgkin's lymphoma patients. So far the lesions of deletion are in the kinetochore localization domain of the hBUB1 gene that may explain why the deletion lesions in the BUB1 gene cause aneuploidy in lymphoma and lymphoma cells. The deletions are heterozygous in nature. Like the mutated hBUB1 gene in colorectal cancer, the mutant hBUB1 cDNA from lymphoblastic leukemia cells behaves dominantly.