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Integration of conventional cytogenetics (G-banding), comparative genomic hybridization (CGH) and interphase fluorescence in situ hybridization (i-FISH) for the detection of genomic rearrangements in acute leukemia
  1. Peter McGrattan (peter.mcgrattan{at}belfasttrust.hscni.net)
  1. Northern Ireland Regional Genetics Centre, Northern Ireland
    1. Sabrina-Leigh Campbell
    1. Queen's University Belfast, Northern Ireland
      1. Robert Cuthbert
      1. Department of Haematology, Belfast City Hospital, Northern Ireland
        1. Francis GC Jones
        1. Haematology, Belfast City Hospital, Northern Ireland
          1. Mary F McMullin
          1. Haematology, Belfast City Hospital, Northern Ireland
            1. Mervyn Humphreys
            1. Northern Ireland Regional Genetics Centre, Northern Ireland

              Abstract

              Aims: To screen for genomic imbalances in patients with acute leukemia using conventional (G-banding) and molecular (CGH and FISH) methods to see if an integrative screening approach increases abnormality detection rate. Methods: G-banded analysis was performed on unstimulated BM or PB cells after short-term (24-hour) culture. CGH was performed on reference (control) and neoplastic (test patient) genomic DNA extracted from BM or PB samples. i-FISH was selectively carried out at disease diagnosis on AML and ALL patients using conventional methods. Results: Genomic rearrangements were detected in 4, 7 and 6 patients using G-banding, CGH and i-FISH respectively. Discordance in results between G-banding, CGH and/or i-FISH was found in 7 of the 12 patients screened. G-banding and CGH, when used individually, detected a genomic imbalance/rearrangement in 33.3% and 58.3% of the patients screened respectively. However, when both screening methods were integrated, the abnormality detection rate increased to 66.7%. This detection rate increased further to 75.0% with the use of i-FISH screening. Conclusions: The advantages and disadvantages of using G-banding, CGH and i-FISH as either stand alone or integrated screening methods for the detection and characterization of genomic imbalances in acute leukemia are clearly demonstrated. Abnormality detection rate significantly increased when an integrated screening approach was employed which could potentially provide valuable information for risk stratification in patients with acute leukemia.

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