Array comparative genomic hybridization and cytogenetic analysis in pediatric acute leukemias

Cytogenetics Laboratory, Diagnostic Services Manitoba, Winnipeg, MB.
Current Oncology (Impact Factor: 1.79). 10/2011; 18(5):e210-7. DOI: 10.3747/co.v18i5.770
Source: PubMed


Most patients with acute lymphocytic leukemia (all) are reported to have acquired chromosomal abnormalities in their leukemic bone marrow cells. Many established chromosome rearrangements have been described, and their associations with specific clinical, biologic, and prognostic features are well defined. However, approximately 30% of pediatric and 50% of adult patients with all do not have cytogenetic abnormalities of clinical significance. Despite significant improvements in outcome for pediatric all, therapy fails in approximately 25% of patients, and these failures often occur unpredictably in patients with a favorable prognosis and "good" cytogenetics at diagnosis.It is well known that karyotype analysis in hematologic malignancies, although genome-wide, is limited because of altered cell kinetics (mitotic rate), a propensity of leukemic blasts to undergo apoptosis in culture, overgrowth by normal cells, and chromosomes of poor quality in the abnormal clone. Array comparative genomic hybridization (acgh-"microarray") has a greatly increased genomic resolution over classical cytogenetics. Cytogenetic microarray, which uses genomic dna, is a powerful tool in the analysis of unbalanced chromosome rearrangements, such as copy number gains and losses, and it is the method of choice when the mitotic index is low and the quality of metaphases is suboptimal. The copy number profile obtained by microarray is often called a "molecular karyotype."In the present study, microarray was applied to 9 retrospective cases of pediatric all either with initial high-risk features or with at least 1 relapse. The conventional karyotype was compared to the "molecular karyotype" to assess abnormalities as interpreted by classical cytogenetics. Not only were previously undetected chromosome losses and gains identified by microarray, but several karyotypes interpreted by classical cytogenetics were shown to be discordant with the microarray results. The complementary use of microarray and conventional cytogenetics would allow for more sensitive, comprehensive, and accurate analysis of the underlying genetic profile, with concomitant improvement in prognosis and treatment, not only for pediatric all, but for neoplastic disorders in general.

Download full-text


Available from: Angelika J Dawson, Jun 10, 2014
  • Source
    • "Complementary techniques to conventional cytogenetics such as fluorescence in situ hybridization (FISH), and reverse transcriptase - polymerase chain reaction (RT-PCR) can be used as screening tools for ETV6/RUNX1-positive patients [8]. FISH study is useful to identify specific translocation, but it is limited to the type of probe used to bind the genomic region of interest, and is not genome-wide [9]. Array comparative genomic hybridization (array CGH) has been applied to study copy number alterations and genomic imbalances for evaluation of patients with ALL [10]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Acute lymphoblastic leukemia (ALL) is a heterogeneous form of hematological cancer consisting of various subtypes. We are interested to study the genetic aberration in precursor B-cell ALL with specific t(12;21) translocation in childhood ALL patients. A high resolution 244K array-based Comparative Genomic Hybridization (array-CGH) was used to study eleven ETV6/RUNX1-positive childhood acute lymphoblastic leukemia (ALL) patients. Result 155 chromosomal aberrations (119 losses, 36 gains) were reported in the array findings, corresponding to 76.8% deletions and 23.2% amplifications. The ETV6 gene deletion occurred in 4 of the patients, corresponding to 45% of the sample. The most common alterations above 1 Mb were deletion 6q (13%), 12p (12%) and 9p (8%), and duplication 4q (6%) and Xq (4%). Other genes important in ALL were also identified in this study including RUNX1, CDKN2A, FHIT, and PAX5. The array-CGH technique was able to detect microdeletion as small as 400 bp. Conclusion The results demonstrate the usefulness of high resolution array-CGH as a complementary tool in the investigation of ALL.
    Full-text · Article · Nov 2012 · Molecular Cytogenetics
  • [Show abstract] [Hide abstract]
    ABSTRACT: Array comparative genomic hybridization has proven to be a very powerful tool in searching for new biomarkers which can find an application in clinical practise. CGH-array technology is satisfying in almost every possible way. It is highly specific, sensitive, simple, and relatively cheap. Thus, this modern method meets the demands of clinical application. An increasing knowledge about molecular pathways and pathologic genome alterations in acute leukemias enable to define unequivocal diagnosis, prognosis and to predict a response to individual compatible therapy. This review shows a various application of CGH-array in pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
    No preview · Article · Jun 2013 · Pediatric Hematology and Oncology