Trisomy 12 was described in the early 1980s as the first recurrent aberration in B-CLL; with a prevalence between 10 and 25%, it was among the most frequent aberrations in nearly all subsequent studies using chromosome banding (14,20,30,68-73). However, the identification of a critical region remained difficult, since usually a complete additional chromosome 12 was present and partial trisomy was observed only in very rare cases (17,68,74).
Molecular cytogenetics by interphase FISH was used in numerous studies to detect trisomy 12 in B-CLL and revealed incidences of 10-20% in European studies and more than 30% in two US studies (17,75-82) (Table 1). The observation of one case of B-CLL with isolated over-representation of bands 12q13-q14 is interesting with respect to identification of a critical segment on chromosome 12 (83). Merup et al. (84) examined a tumor with a complex 12q rearrangement and that found bands 12q13-q15 were most frequently amplified. Dierlamm et al. (85) observed partial trisomy 12 using FISH in 11 of more than 1000 lymphomas. Bands 12q13-q22 were the smallest mutually duplicated segment in four B-CLL cases in this series. Among others, genes of oncogenic potential, like CDK4, GLI, and MDM2, are localized in this genomic region, but no pathogenetic relevance for B-CLL has been shown to date for any of these genes. Currently the innovative approach of DNA microarray chip technology is being used, employing matrix comparative genomic hybridization (CGH) for identification of the smallest replicated genomic regions in bands 12q13-q21 in B-CLL (86-89) (Fig. 4).
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