) A major role of the Cytogenetics Core will be to establish a cytogenetic profile for all acute lymphoblastic leukemias (ALL) studied by the project group. The """"""""entry point"""""""" cytogenetic profile, for all patients enrolled in clinical studies, will include fluorescence in situ hybridization (FISH) determination of t(9;22) [BCR-ABL]; t(12;21) [TEL-AML1]; 11q23 rearrangement [MLL]; t(1;19) [E2A-PBX1], 6q21 deletion, 9p21 deletion; and 12p13 deletion. These FISH characterizations will serve as the basis for correlations with patient outcome in Projects 10 and 4. The prognostic relevance of individual chromosomal aberrations, and of the cytogenetic profile, will be evaluated in the context of the various clinical studies. The """"""""entry point"""""""" FISH characterizations will also provide key reference points for the biology-oriented projects. Namely, the FISH evaluations will establish genomic correlates for ALL gene expression patterns (Project 8), and will identify subsets of ALL with 11q23 (MLL) rearrangements (Project 6), 6q, 9p and 12p13 deletions (Project 7), and TEL-AML1 fusions (Project 5). Another function of the core will be provision of an interactive molecular cytogenetic infrastructure for the program. To this end, the core will use molecular cytogenetic assays, including FISH, M-FISH, and comparative genomic hybridization (CGH) to evaluate genomic mechanisms for altered gene or protein expression. Routine clinical karyotyping will not be a function of the core. However, the core will be responsible for centralized review of leukemia karyotypes obtained for all study patients. In addition, the core will perform adjunct molecular cytogenetic evaluations, including unique-sequence FISH, chromosome painting/M-FISH, and CGH, in cases where the external karyotyping studies are ambiguous.
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