PMID- 26136832 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150703 LR - 20220408 IS - 1755-8166 (Print) IS - 1755-8166 (Electronic) IS - 1755-8166 (Linking) VI - 8 DP - 2015 TI - High rates of submicroscopic aberrations in karyotypically normal acute lymphoblastic leukemia. PG - 45 LID - 10.1186/s13039-015-0153-4 [doi] LID - 45 AB - BACKGROUND: 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. RESULTS: Sixty-one 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, dup(18)(q21.2q21.2) with the DCC gene was present in 9 % of the cases, and the CDK6 gene in 7q21.2 was deleted in 12 % of the here in detail studied ALL cases. CONCLUSIONS: In conclusion, high resolution molecular cytogenetic tools and molecular approaches like MLPA and aCGH need to be combined in a cost-efficient way, to identify disease and progression causing alterations in ALL, as majority of them are cryptic in banding cytogenetic analyses. FAU - Othman, Moneeb A K AU - Othman MA AD - Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany. FAU - Melo, Joana B AU - Melo JB AD - Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal ; CIMAGO, Centro de Investigacao em Meio Ambiente, Geneticae Oncobiologia, Coimbra, Portugal. FAU - Carreira, Isabel M AU - Carreira IM AD - Laboratory of Cytogenetics and Genomics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal ; CIMAGO, Centro de Investigacao em Meio Ambiente, Geneticae Oncobiologia, Coimbra, Portugal. FAU - Rincic, Martina AU - Rincic M AD - Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany ; Croatian Institute of Brain Research, Zagreb, Croatia. FAU - Glaser, Anita AU - Glaser A AD - Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany. FAU - Grygalewicz, Beata AU - Grygalewicz B AD - Cytogenetic Laboratory, Maria Sklodowska-Curie Memorial Cancer Centre and Institute, Warsaw, Poland. FAU - Gruhn, Bernd AU - Gruhn B AD - Department of Pediatrics (Oncology and Hematology), Jena University Hospital, Friedrich Schiller University, Jena, Germany. FAU - Wilhelm, Kathleen AU - Wilhelm K AD - Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany ; Department of Pediatrics (Oncology and Hematology), Jena University Hospital, Friedrich Schiller University, Jena, Germany. FAU - Rittscher, Katharina AU - Rittscher K AD - Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany. FAU - Meyer, Britta AU - Meyer B AD - ZytoVision GmbH, Bremerhaven, Germany. FAU - Silva, Maria Luiza Macedo AU - Silva ML AD - Cytogenetics Department, Bone Marrow Transplantation Unit, National Cancer Institute, Rio de Janeiro, RJ Brazil ; Post Graduation Program in Oncology, National Cancer Institute (INCA), Rio de Janeiro, RJ Brazil. FAU - de Jesus Marques Salles, Terezinha AU - de Jesus Marques Salles T AD - Pediatric Oncohematology Center, Hospital Oswaldo Cruz/ Pos Graduation Course of the Faculty of Medical Sciences, University of Pernambuco, Recife, PE Brazil. FAU - Liehr, Thomas AU - Liehr T AD - Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany. LA - eng PT - Journal Article DEP - 20150630 PL - England TA - Mol Cytogenet JT - Molecular cytogenetics JID - 101317942 PMC - PMC4486437 OTO - NOTNLM OT - Acute lymphoblastic leukemia (ALL) OT - Array-comparative genomic hybridization (aCGH) OT - Cryptic rearrangements OT - Fluorescence in situ hybridization (FISH) OT - Multiplex ligation-dependent probe amplification (MLPA) OT - Multitude multicolor banding (mMCB) EDAT- 2015/07/03 06:00 MHDA- 2015/07/03 06:01 PMCR- 2015/06/30 CRDT- 2015/07/03 06:00 PHST- 2015/06/04 00:00 [received] PHST- 2015/06/20 00:00 [accepted] PHST- 2015/07/03 06:00 [entrez] PHST- 2015/07/03 06:00 [pubmed] PHST- 2015/07/03 06:01 [medline] PHST- 2015/06/30 00:00 [pmc-release] AID - 153 [pii] AID - 10.1186/s13039-015-0153-4 [doi] PST - epublish SO - Mol Cytogenet. 2015 Jun 30;8:45. doi: 10.1186/s13039-015-0153-4. eCollection 2015.