Molekulárně cytogenetická analýza komplexních chromosomových aberací u nemocných s MDS a AML. Identifikace chromosomů a chromosomových oblastí zahrnutých v komplexních karyotypech. Zhodnocení prognostického významu komplexních přestaveb.; Molecular cytogenetic analysis of complex chromosomal aberrations in patients with MDS and AML. Identification of chromosomes and/or chromosomal regions involved in complex karyotypes. Evaluation of the impact of complex rearrangements on prognosis of the patients.

• MeSH
• akutní myeloidní leukemie MeSH
• chromozomální aberace MeSH
• cytogenetika MeSH
• hybridizace in situ fluorescenční MeSH
• myelodysplastické syndromy MeSH
• prognóza MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• hematologie a transfuzní lékařství
• onkologie
• biologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

Gene amplification is a frequent genetic abnormality in solid tumors, and many oncogenes are activated in this way. In acute myeloid leukemia (AML), a frequent target of gene amplification is chromosome 11, particularly chromosome region 11q23, including the MLL (myeloid/lymphoid leukemia) gene. However, the number of other amplicons from the long arm of chromosome 11 has also been described. Duplication/amplification of chromosome 11 was found by cytogenetic methods in 10 of 119 newly diagnosed patients with AML. The amplification was presented as: amplification including only the 5' segment of the MLL gene (1 patient), trisomy 11 (3 patients), partial trisomy 11q (2 patients), isochromosome 11q (1 patient), and multiple amplification of specific regions (3 patients). In two cases, amplification involved parts of not only long arm but also of short arm of the chromosome 11: 11p15 and 11p11.1 to 11p13.

• MeSH
• akutní myeloidní leukemie diagnóza   genetika   MeSH
• amplifikace genu MeSH
• dospělí MeSH
• duplikace genu MeSH
• hybridizace in situ fluorescenční MeSH
• karyotypizace MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 11 genetika   MeSH
• prognóza MeSH
• senioři MeSH
• trizomie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Molecular-cytogenetic methods were used to analyse and specify complex genome rearrangements in malignant cells. Twelve samples of bone marrow cells were collected from patients with myelodysplastic syndromes (MDS). The complex karyotypes were examined by multicolour fluorescence in situ hybridization (mFISH), high-resolution multicolour banding (mBAND) and array comparative genomic hybridization (aCGH). For aCGH, DNA was isolated from fixed bone marrow cells in methanol and acetic acid and amplified by whole-genome amplification. Three samples were analysed by the oligonucleotide array NimbleGen on the basis of full service. BAC-based Haematochips (BlueGnome) were used for the other nine samples. Sensitivity and detection limits of both methods were compared. The results obtained by mFISH/mBAND were in most cases confirmed by the microarray technique. aCGH detected 43 unbalanced chromosomal changes that were also identified by classical cytogenetics and FISH. Moreover, aCGH discovered 14 additional changes. Cryptic amplifications and deletions were characterized with a resolution of 0.5 Mb. In one bone marrow sample with suspected monosomy 5 detected by conventional cytogenetic analysis, aCGH revealed a 22.3 Mb region of chromosome 5 inserted in another autosome within the complex karyotype. Amplified DNA was successfully used for aCGH in 11 out of 12 cases, improving resolution of unbalanced chromosomal aberrations. The combination of both approaches brought more detailed description of complex karyotypes and is highly recommended.

• MeSH
• cytogenetika metody   přístrojové vybavení   MeSH
• dospělí MeSH
• financování organizované MeSH
• genová přestavba MeSH
• hybridizace in situ fluorescenční MeSH
• karyotypizace metody   MeSH
• lidé MeSH
• lidské chromozomy, pár 5 MeSH
• myelodysplastické syndromy genetika   MeSH
• srovnávací genomová hybridizace metody   přístrojové vybavení   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH

• Publikační typ
• abstrakty MeSH

Unusual MLL gene rearrangements were found in bone marrow cells of four patients with acute myeloid leukemia. A combination of conventional and molecular cytogenetic methods were used to describe translocations t(9;12;11)(p22;p13;q23), t(11;19)(q23;p13.3), and t(10;11)(p12;23) and inverted insertion ins(10;11)(p12;q23.3q23.1). Partial nontandem duplication of the MLL gene was identified by reverse transcriptase-polymerase chain reaction in all cases. The duplication, which included MLL exons 2 through 8-9, was interrupted by a cryptic insertion of one or two exons from the respective MLL partner gene: MLLT10, MLLT3, or MLLT1.

• MeSH
• akutní myeloidní leukemie genetika   MeSH
• DNA primery MeSH
• dospělí MeSH
• duplikace genu MeSH
• hybridizace in situ fluorescenční MeSH
• kojenec MeSH
• lidé MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• protoonkogenní protein MLL genetika   MeSH
• sekvence nukleotidů MeSH
• translokace genetická MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH