CC BY
19
Раздел 2 Педиатрия
HC15 gene in intellectual impairment. Overall, revealing the disruption of an X-linked intellectual disability-related gene in patients with balanced X-autosome translocation is a useful tool for the better characterization of critical genes for neurodevelopment. This approach might be a valuable resource when applied not only in patients with cognitive impairment, but also in subjects with normal cognition.
A NEW IGH@ GENE REARRANGEMENT ASSOCIATED WITH CDKN2A/B DELETION IN A YOUNG ADULT B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (BALL)
Othman M.A.K.1, Grygalewicz B.2, Pienkowska-Grela B.3, Ejduk A.3, Rincic M.1-4, Melo J.5-6, Carreira I. M.5-6, Meyer B.7, Marzena W.8, Liehr T.1 'Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany 2Cytogenetic Laboratory, Maria Sklodowska-Curie Memorial Cancer Centre and Institute, Warsaw, Poland 3Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland "Croatian Institute of Brain Research, Zagreb, Croatia 5Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal 6CIMAGO, Centro de Investigagao em Meio Ambiente, Geneticae Oncobiologia 7ZytoVision GmbH, Bremerhaven, Germany 8Department of Haematology and Bone Marrow Transplantation, Holycross Cancer Center, Kielce, Poland
Acquired copy number changes are common in acute leukemia. They are reported as recurrent amplification or deletion and may be indicative for involvement of oncogenes or tumor suppressor genes in the acquired disease and can serve as potential biomarkers for prognosis or even as a target for molecular therapy. Here, we report a gain of copy numbers of 14ql3 to 14q32 leading to an IGH@ locus splitting in a young adult female, present as a yet unreported rearrangement in B-cell acute lymphoblastic leukemia (B-ALL). Low resolution banding cytogenetics at the time of diagnosis revealed a normal karyotype. However, retrospective application of fluorescence in situ hybridization-(FISH-) banding, locus specific FISH-probes, as well as multiplex ligation-dependent probe amplification and high resolution array-comparative genomic hybridization revealed previously cryptic aberrations. Overall a karyotype 46,XX,del(9)(p21.3p21.3),der(14)(pter->q32.33::q32.33->q13::q32.33->qter) was determined. The patient was treated according to PALG 5-ALL7-3 protocol and achieved complete remission. These findings indicate that a favorable prognosis is linked to these aberrations under the mentioned treatment. Supported in parts by the DAAD.
HIGH RATES OF SUBMICROSCOPIC ABERRATIONS IN KARYOTYPICALLY NORMAL ACUTE LYM-PHOBLASTIC LEUKEMIA
Othman M.A.K.1, Melo J.B.23, Carreira I.M.2'3, Rincic M.14, Glaser A.1, Grygalewicz B.5, Gruhn B.6, Wilhelm K.16, Rittscher K.1, Meyer B.7, Macedo S.M.L.8~9, de Jesus Marques S.T.10, Liehr T.1
Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany 2Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal 3CIMAGO, Centro de Investigagao em Meio Ambiente, Geneticae Oncobiologia, Coimbra, Portugal 4Croatian Institute of Brain Research, Zagreb, Croatia 5Cytogenetic Laboratory, Maria Sklodowska-Curie Memorial Cancer Centre and Institute, Warsaw, Poland •Department of Pediatrics (Oncology and Hematology), Jena University Hospital, Friedrich Schiller University, Jena, Germany
7ZytoVision GmbH, Bremerhaven, Germany Cytogenetics Department, Bone Marrow Transplantation Unit, National Cancer Institute, Rio de Janeiro, RJ, Brazil
9Post Graduation Program in Oncology, National Cancer Institute (INCA), Rio de Janeiro, Brazil 10Pediatric Oncohematology Center, Hospital Oswaldo Cruz/ Pos Graduation Course of the Faculty of Medical Sciences, University of Pernambuco, Recife, PE, Brazil
Acute lymphoblastic leukemia (ALL) is not a single uniform disease. It consists of several subgroups with different cytogenetic and molecular genetic aberrations, clinical presentations and outcomes. Banding cytogenetics plays a pivotal role in the detection of recurrent chromosomal rearrangements and is the starting point of genetic analysis in ALL, still. Nowadays, molecular (cyto)genetic tools provide substantially to identify previously non-detectable, so-called cryptic chromosomal aberrations in ALL. However, ALL according to banding cytogenetics with normal karyotype — in short cytogenetically normal ALL (CN-ALL) — represent up to ~50% of all new diagnosed ALL cases. The overall goal of this study was to identify and characterize the rate of cryptic alterations in CN-ALL and to rule out if one single routine approach may be sufficient to detect most of the cryptic alterations present. 61 ALL patients with CN-ALL were introduced in this study. All of them underwent high resolution fluorescence in situ hybridization (FISH) analysis. Also DNA could be extracted from 34 ALL samples. These DNA-samples were studied using a commercially available MLPA (multiplex ligation-dependent probe amplification) probe set directed against 37 loci in hematological malignancies and/or array-comparative genomic hybridization (aCGH). Chromosomal aberrations were detected in 21 of 61 samples (~34%) applying FISH approaches: structural abnormalities were present in 15 cases and even numerical ones were identified in 6 cases. Applying molecular approaches copy number alterations (CNAs) were detected in 27/34 samples. Overall, 126 CNAs were identified and only 34 of them were detectable by MLPA (~27%). Loss of CNs was identified in ~80% while gain of CNs was present in ~20% of the 126 CNAs. A maximum of 13 aberrations was detected per case; however, only one aberration per case was found in 8 of all in detail studied 34 cases. Of special interest among the detected CNAs are the following new findings: del(15)(q26.1q26.1) including CHD2 gene was found in 20% of the studied ALL cases,
РОССИЙСКИЙ ВЕСТНИКПЕРИНАТОЛОГИИ И ПЕДИАТРИИ, 4, 2015
