Neocentromere formation in a stable ring 1p32-p36.1 chromosome

Neocentromeres are functional centromeres formed in chromosome regions outs ide the normal centromere domains and are found in an increasing number of mitotically stable human marker chromosomes in both neoplastic and nonneopl astic cells. We describe here the formation of a neocentromere in a previou sly undescribed chromosomal region at 1p32-->p36.1 in an oligospermic patie nt. Cytogenetic GTL banding analysis and the absence of detectable fluoresc ence in situ hybridisation (FISH) signals using telomeric probes indicate t he marker to be a ring chromosome. The chromosome is negative for CBG bandi ng and is devoid of detectable centromeric a satellite and its associated c entromere protein CENP-B, suggesting activation of a neocentromere within t he 1p32-36.1 region. Functional activity of the neocentromere is shown by t he retention of the ring chromosome in 97% of the patient's lymphocytes and 100% of his cultured fibroblasts, as well as by the presence of key centro mere binding proteins CENP-E, CENP-F, and INCENP. These results indicate th at in addition to CENP-A, CENP-C, and CENP-E described in earlier studies, neocentromere activity can further be defined by CENP-F and INCENP binding. Our evidence suggests that neocentromere formation constitutes a viable me chanism for the mitotic stabilisation of acentric ring chromosomes.