Molecular studies of an ependymoma-associated constitutional t(1;22)(p22;q11.2).

We previously described a patient with a de novo constitutional translocation, t(1;22)(p22;q11.2), who developed a malignant ependymoma at age 5, and we proposed that the translocation predisposed the child to the development of the tumor. As a step toward isolation of a putative cancer gene, we have characterized the breakpoints of the (1;22) translocation at the molecular level. The chromosome 22 breakpoint has been narrowed to a region between ARVCF and D22S264. The chromosome 1 breakpoint has been mapped onto a doubly-linked Whitehead YAC contig by PCR analysis of the STS contents of the patient's derivative chromosomes isolated in somatic cell hybrids. Loss-of-heterozygosity (LOH) studies of the patient's ependymoma and of sporadic ependymomas showed no evidence of consistent loss in the breakpoint regions, suggesting that activation of an oncogene, rather than inactivation of a tumor suppressor gene, is the more likely molecular mechanism involved in this case. The gene for Edg-1, a neurally expressed, seven-segment transmembrane receptor, maps to the region of the chromosome 1 breakpoint but does not appear to be interrupted by the translocation. Molecular characterization of the breakpoint regions reported here represents an important step in the identification of the gene(s) affected by this translocation.