The use of m-band to identify dual inversions in chromosome 4
The incidence of chromosomal inversions is reported as 0.12-0.7% for pericentric and 0.1-0.5% for paracentric inversions, excluding inversions involving heterochromatic regions. To date there has been no report of concurrent pericentric and paracentric inversions seen on the one chromosome. In 2005, a 75 year old female presented with essential thrombocythaemia. Bone marrow (BM) chromosome analysis showed an inv(4)(q12q21), in addition to a queried del(4)(p11p12). Peripheral blood (PB) analysis was performed and suggested an inv(4)(p14q12) and inv(4)(q13.2q21.3). The same rearrangements were present in all spreads, suggesting that they were constitutional in origin.
To confirm the rearrangements and chromosomal breakpoints (bp), m-band was applied to chromosome 4 in both BM and PB. M-band uses region specific partial chromosome painting probes, derived by microdissection. Each paint is labelled with a unique fluorochrome combination and partially overlaps its neighbouring probe. The ensuing fluorescence intensity pattern along the chromosome axis results in a continuous change of colour ratios, which, when processed using appropriate software, reveals a reproducible pseudo colour banding pattern. M-band results clearly illustrated two distinct inversions in both the PB and BM. One was confirmed as pericentric at 4p14q12. For the second inversion, m-band assigned more accurate bp with the proximal bp at 4q12, rather than 4q13.2, and the distal bp at 4q22, as opposed to the 4q21.3. Furthermore, m-band revealed that there was no deletion present in the p arm of the inverted chromosome 4 in BM cells.
These results illustrate the power of m-band to detect intra-chromosomal rearrangements. As a supplement to classical cytogenetics, m-band has the potential to extend the limits of chromosomal interpretation. In our case, m-band played a central role in the accurate identification of a novel case of dual inversions.