Genomic Microarrays in Chromosomal Analysis of Leukemia
نویسنده
چکیده
................................................................................................................................ 9 INTRODUCTION ..................................................................................................................... 10 REVIEW OF THE LITERATURE ......................................................................................... 11 1. Cancer and genetic alterations ................................................................................................. 11 2. Chromosomal imbalances in cancer ........................................................................................ 12 2.1. Translocations and inversions .......................................................................................... 13 2.2. DNA copy number losses ................................................................................................ 13 2.3. Amplifications ................................................................................................................. 14 2.4. Loss of heterozygosity ..................................................................................................... 15 2.5. Uniparental disomy .......................................................................................................... 16 3. Microarrays in the analysis of chromosomal imbalances ....................................................... 17 3.1. Array comparative genomic hybridization ...................................................................... 17 3.2. Single-nucleotide polymorphism microarray analysis ..................................................... 19 4. Leukemia ................................................................................................................................. 22 4.1. Acute myeloid leukemia .................................................................................................. 22 4.1.1. Clinical characteristics and treatment of acute myeloid leukemia .......................... 22 4.1.2. Genetic alterations in acute myeloid leukemia ....................................................... 24 4.2. Chronic lymphocytic leukemia ........................................................................................ 27 4.2.1 Clinical characteristics and treatment of chronic lymphocytic leukemia ................ 27 4.2.2. Genetic alterations in chronic lymphocytic leukemia ............................................. 28 AIMS OF THE STUDY ............................................................................................................ 31 MATERIALS AND METHODS .............................................................................................. 32 1. Specimens (I-IV) ..................................................................................................................... 32 1.1. Acute myeloid leukemia specimens ................................................................................. 32 1.2. Chronic lymphocytic leukemia specimens ...................................................................... 32 2. Complementary DNA array comparative genomic hybridization (I) ...................................... 33 3. Oligonucleotide array comparative genomic hybridization (I-III) .......................................... 33 4. Fluorescence in situ hybridization (I, II) ................................................................................. 34 5. Gene expression (I) ................................................................................................................. 35 6. Mutation analysis (II) .............................................................................................................. 35 7. Loss of heterozygosity analysis with single-nucleotide polymorphism microarray (IV) ....... 35 RESULTS AND DISCUSSION ................................................................................................ 37 1. Characterization of 11q amplicons in acute myeloid leukemia (I) .......................................... 37 2. Cryptic copy number changes in karyotypically normal acute myeloid leukemia (II) ........... 40 3. Array comparative genomic hybridization in chronic lymphocytic leukemia (III) ................. 42 4. Loss of heterozygosity in karyotypically normal acute myeloid leukemia (IV) ..................... 44 CONCLUSIONS ....................................................................................................................... 47 ACKNOWLEDGMENTS ........................................................................................................ 50 REFERENCES .......................................................................................................................... 51
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