Molecular analysis of the aberrant replication banding pattern on chromosome 15 in murine T-cell lymphomas

Cytogenetic techniques revealed an altered early replication banding pattern on the distal part of chromosome 15 in some murine T-cell lymphomas. This pattern reverted back to normal replication in somatic cell hybrids that had become non-tumorigenic after fusion of leukemic cells with normal fibroblasts. The altered banding pattern was correlated with malignancy. To investigate the molecular basis of the aberrant pattern in more detail, centrifugal elutriation of cells containing bromodeoxyuridine labeled DNA was used to prepare newly replicated DNA from selected intervals of the S-phase from tumor cells, as well as from hybrid cells with the revertant phenotype. These different DNA fractions were probed for DNA sequences distributed over the distal half of chromosome 15. Only two out of ten chromosome 15 specific genes tested showed a clear change in replication timing between the two different cell lines tested. These two genes were the lymphocyte antigen-6, Ly-6, and the neighboring thyroglobulin gene, Tgn, which replicated at the beginning of S in the tumor cells and later in S in the non-tumorigenic hybrid cells.