Mapping of the breakpoints on the short arm of chromosome 17 in neoplasms with an i(17q)

Isochromosomes are monocentric or dicentric chromosomes with homologous arm s that are attached in a reverse configuration as mirror images. With an in cidence of 3-4%, the i(17q) represents the most frequent isochromosome in h uman cancer. It is found in a variety of tumors, particularly in blast cris is of chronic myeloid leukemia (CML-BC), acute myeloid leukemia (AML), non- Hodgkin's lymphoma (NHL), and medulloblastoma (MB), and indicates a poor pr ognosis. To determine the breakpoints on the molecular genetic level, we an alyzed 18 neoplasms (six CML, four AML, one NHL, and seven MB) with an i(17 q) and two MB with a pure del(17p) applying fluorescence in situ hybridizat ion (FISH) with yeast artificial chromosome (YAC) clones, PI-artificial chr omosome (PAC) clones, and cosmids from a well-characterized contig covering more than 6 Mb of genomic DNA. We identified four different breakpoint clu ster regions. One is located close to or within the centromere of chromosom e 17 and a second in the Charcot-Marie-Tooth (CMTIA) region at 17(p11.2), A third breakpoint was found telomeric to the CMTIA region. The fourth, most common breakpoint was detected in MB, AML, and in CML-BC specimens and was bordered by two adjacent cosmid clones (clones D14149 and M0140) within th e Smith-Magenis syndrome (SMS) region. These results indicate that the low copy number repeat gene clusters which are present in the CMT and SMS regio ns may be one of the factors for the increased instability that may trigger the formation of an i(17q). (C) 1999 Wiley-Liss, Inc.