The Principles of Clinical Cytogenetics - Extra Materials - Springer

468 Daynna Wolff and Stuart Schwartz
Fig. 8. Metaphases from an XX sex-reversed male were hybridized with probes for the X centromere (green)
and a probe for the SRY gene (red). Results demonstrated a cryptic translocation in which SRY was present on
the short arm of one X chromosome. Chromosomes were counterstained blue with DAPI.
p13. The fusion product interferes with the core-binding transcription pathway that is needed for
normal hematopoiesis. Break-apart (BAP) FISH probes have been developed that bind to the 3' and 5'
regions of the CBFβ gene, producing a yellow fusion signal in the normal situation and a single red
and a single green signal when the gene is disrupted by inversion or translocation. Given that the
inversion produces a subtle change in the banding pattern of chromosome 16, the aberration is often
difficult to distinguish using routine cytogenetics, particularly for cases with suboptimal chromosome
preparations. Thus, FISH or other molecular techniques are recommended for definitive diagnostic
and residual disease assessments.
Abnormalities of the MLL gene are seen in a small percentage of AML and are common in acute
lymphoid leukemias (ALL). The majority of rearrangements of 11q23 involve the translocation of
the 5' region of MLL to the 3' region of a partner gene. Over 30 different partner genes have been
identified and FISH provides an efficient screen for detection of all aberrations involving MLL.
Dual-color break-apart probes that span the 5' and 3' regions of the gene produce a yellow fusion
signal for the normal situation with no disruption of the MLL gene, or a single red and a single
green signal when any translocation involving MLL has occurred (see Fig. 9). In addition, the BAP
allows for the assessment of copy number of MLL to determine if deletions or duplications of the
gene have occurred.