Identification of der(1;19)(q10;p10) in 5 oligodendrogliomas suggests mechanism of concurrent 1p and 19q loss characteristic of this tumor. L. Morsberger, K. Murphy, P. Burger, C. Griffin. Dept of Pathology, Johns Hopkins University, Baltimore, MD.
   Deletions of portions of chromosomes 1p and 19q are closely associated with the oligodendroglioma (OG) histological phenotype. In most cases, 1p and 19q are co-deleted, often involving the entire chromosomal arm, yet the mechanism of dual loss is unexplained and the few reported metaphase cytogenetic analyses of OG have not elucidated this. We have analyzed 5 cases of OG (WHO grade III) in which metaphase cytogenetics suggests a possible mechanism for concurrent 1p and 19q loss. The G-banded metaphases of 4 OGs were near diploid and included a derivative chromosome consisting of what appears to be the whole arms of 1q and 19p joined at the centromere forming a der(1;19)(q10;p10). A fifth case was near tetraploid and contained 2 or more copies of the derivative chromosome. Metaphase FISH with 1p, 1q, 19p, and 19q probes (Vysis/Abbott Molecular) confirmed loss of 19q and 1p and that the derivative chromosome was composed of 1q and 19p material in 3 cases; in 2 cases with few metaphases, FISH was limited to the 19p/19q probe set where we found loss of 19q, and presence of 19p material on the derivative chromosome. In all cases, interphase FISH showed net loss of 1p and 19q in 77-92% of cells. Microsatellite studies were consistent with 1p and 19q loss in 4 cases and are pending in 1. To our knowledge this is the first report of metaphase cytogenetic analysis of OG identifying a derivative chromosome comprised of 1q and 19p. We hypothesize that the following occurs in OG: formation of a balanced whole-arm translocation between chromosomes 1 and 19, forming two derivative chromosomes, one composed of 1q and 19p, the other composed of 1p and 19q. Subsequent loss of the der(1;19)(p10;q10) would then result in the simultaneous 1p and 19q loss observed in OG, with retention of the der(1;19)(q10;p10) as observed in these 5 OGs.