Computer aided analysis of additional chromosome aberrations in Philadelphia chromosome positive acute lymphoblastic leukaemia using a simplified computer readable cytogenetic notation

Background: The analysis of complex cytogenetic databases of
distinct leukaemia entities may help to detect rare recurring
chromosome aberrations, minimal common regions of gains and losses,
and also hot spots of genomic rearrangements. The patterns of the
karyotype alterations may provide insights into the genetic
pathways of disease progression. Results: We developed a simplified
computer readable cytogenetic notation (SCCN) by which chromosome
findings are normalised at a resolution of 400 bands. Lost or
gained chromosomes or chromosome segments are specified in detail,
and ranges of chromosome breakpoint assignments are recorded.
Software modules were written to summarise the recorded chromosome
changes with regard to the respective chromosome involvement. To
assess the degree of karyotype alterations the ploidy levels and
numbers of numerical and structural changes were recorded
separately, and summarised in a complex karyotype aberration score
(CKAS). The SCCN and CKAS were used to analyse the extend and the
spectrum of additional chromosome aberrations in 94 patients with
Philadelphia chromosome positive (Ph-positive) acute lymphoblastic
leukemia ( ALL) and secondary chromosome anomalies. Dosage changes
of chromosomal material represented 92.1% of all additional events.
Recurring regions of chromosome losses were identified. Structural
rearrangements affecting ( peri) centromeric chromosome regions
were recorded in 24.6% of the cases. Conclusions: SCCN and CKAS
provide unifying elements between karyotypes and computer
processable data formats. They proved to be useful in the
investigation of additional chromosome aberrations in Ph-positive
ALL, and may represent a step towards full automation of the
analysis of large and complex karyotype databases.