Cytogenetic, molecular, and array-based analysis of a complex translocation found in a patient diagnosed with CLL
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Authors
Gallogly, Shane
Date of Issue
2011-04-01
Type
thesis
Language
Subject Keywords
chronic lymphocytic leukemia, tumor suppressor genes, chromosomal abnormality, chromosomes
Other Titles
Abstract
Although a number of genes and chromosomal abnormalities have been associated with the presence of chronic lymphocytic leukemia (CLL), no oncogenes or critical tumor suppressor genes (TSGs) have yet been implicated in its onset. In this study, we describe a chromosomal abnormality existing in a subset of white blood cells from an individual experiencing early stages of CLL: a balanced rearrangement involving the p-arms of chromosomes 1, 3, and 6. This mutation being both unique and balanced suggests that the genes disrupted by the translocation breakpoints may be critical to the initiation of CLL. Microdissection techniques were used to physically isolate chromosomal breakpoint regions, which were then analyzed via array comparative genomic hybridization and results confirmed by fluorescence in-situ hybridization. The translocation breakpoints were narrowed to contain WAS protein family member 2 (WASF2), AT hook DNA binding motif (AHDC1), and Gardner-Rasheed feline sarcoma viral oncogene homolog (FGR) genes on chromosome 1, a TSG cluster on chromosome 3, and the UHRF1 binding protein 1 (UHRF1BP1) gene on chromosome 6. Earlier research found that the FGR gene and 3p21.3 TSG cluster have properties that may promote neoplastic tendencies during abnormal expression. In conclusion, we suggest one or more of these genes is a candidate for initial and/or early development of CLL. Future work will be focused on further narrowing the breakpoints of this rearrangement and studying cellular implications involved in abnormal expression of these candidate genes.