Molecular cloning of the translocation breakpoint in T-ALL 11;14 (p13;q11): genomic map of TCR alpha and delta region on chromosome 14q11 and long-range map of region 11p13

Abstract

Using chromosome walking techniques, overlapping lambda and cosmid clones from the T cell receptor alpha (TCRα) region have been isolated; these span the entire Jα region and parts of the TCR delta gene. Molecular analysis of the acute childhood leukemia cells (T-ALL) 8511 revealed a rearrangement on one chromosome 14 in Jα 58 kb 5′ of Cα; this does not result in production of α message. The translocation was identified 90 kb 5′ of Cα at the previously identified Jδ² element. A probe derived from the 5′ region of the translocation breakpoint hybridized to DNA from a mouse-human cell hybrid containing chromosome 11 as the only human chromosome. This probe was used to isolate cosmid clones from chromosome 11. Several rare cutting restriction enzyme sites were found in close vicinity to the translocation breakpoint, and a long-range map spanning 1000 kb of chromosome region 11p13 was established. Analysis of the DNA from 15 cases of sporadic and familial Wilms' tumor did not reveal any changes, indicating that the translocation breakpoint does not reside in this gene.