Spectral karyotyping and interphase FISH reveal abnormalities not detected by conventional G‐banding

Abstract

Seventy uniformly treated children with acute lymphoblastic leukemia were analysed for chromosomal abnormalities with conventional G-banding, spectral karyotyping (SKY) and interphase fluorescent in situ hybridisation (FISH) using probes to detect MLL, BCR/ABL, TEL/AML1 rearrangements and INK4 locus deletions. Numerical and/or structural changes could be identified in 80% of the patients by the use of molecular cytogenetic techniques, whereas abnormalities could be detected in 60% of the patients using G-banding alone. Altogether, 106 structural aberrations were defined by FISH compared to 34 using G-banding. Seventy-four percent of the patients had numerical aberrations, 54% structural aberrations and 20% had no identified aberrations. Twelve cases had prognostically unfavourable chromosomal aberrations that had not been detected in the G-banded analysis. We identified three novel TEL partner breakpoints on 1q41, 8q24 and 21p12, and a recurrent translocation t(1;12)(p32;p13) was found. In addition, two cases displayed amplification (7-15 copies) of AML1. Our results demonstrate the usefulness of SKY and interphase FISH for the identification of novel chromosome aberrations and cytogenetic abnormalities that provide prognostically important information in childhood ALL.

Combined high-resolution array-based comparative genomic hybridization and expression profiling of ETV6/RUNX1-positive acute lymphoblastic leukemias reveal a high incidence of cryptic Xq duplications and identify several putative target genes within the commonly gained region

“…According to the Mitelman database of chromosome aberrations in cancer, 26 only four such translocations have previously been described in childhood ALL. [15][16][17]30 Interestingly, three of these cases were ETV6/RUNX1 positive. 16,17,30 None of these abnormalities had been identified by G-banding; hence, it is possible that, owing to the similar banding pattern of the involved chromosome arms in combination with the poor banding quality often found in childhood ALL, der(6)t(X;6) and der(11)t(X;11) may go undetected unless specifically looked for by FISH.…”

“…14 To the best of our knowledge, only eight ETV6/RUNX1-positive ALLs with partial Xq gains, as identified by metaphase CGH or multicolor FISH, have been described. [15][16][17][27][28][29] All the gains in these cases were generated through unbalanced translocations involving Xq, none of which were seen by conventional cytogenetics. Notably, all cases with Xq gain in the present study were males, as were six of the previously published cases; 16,17,[27][28][29] the gender of the remaining two cases was not reported.…”

“…14 Apart from the additional 12p and 21q abnormalities, often found by FISH with probes specific for ETV6 and RUNX1, most of the secondary abnormalities have been detected by chromosome banding analyses alone, or in some instances by multicolor FISH. [15][16][17] Because of the limited resolution level of these methods, many small-and all cytogenetically cryptic-genomic imbalances of possible prognostic and pathogenetic importance have so far gone undetected.…”

Spectral karyotyping of human, mouse, rat and ape chromosomes – applications for genetic diagnostics and research

“…The power of the SKY technique was again demonstrated when stratified cohorts of childhood B-lineage acute lymphoblastic leukemias (B-ALLs) with more than 150 patients were re-evaluated subsequently to chromosome banding (Elghezal et al, 2001;Mathew et al, 2001;Nordgren et al, 2002). Twelve of 70 ALL patients showed prognostically unfavourable chromosomal aberrations that were missed before (Nordgren et al, 2002).…”

ABL oncogene amplification with p16INK4a gene deletion in precursor T‐cell acute lymphoblastic leukemia/lymphoma: Report of the first case

“…A growing line of evidence shows that the p16 INK4a deletion heralds poor prognosis of the disease [7]. Detection of the p16 INK4a deletion needs incorporation of a molecular cytogenetic approach such as fluorescence in situ hybridization (FISH), as the deletion may be submicroscopic [8].…”