1. ALLELIC IMBALANCE IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKAEMIA (ALL): APPLICATION OF SINGLE NUCLEOTIDE POLYMORPHISMS ARRAY (SNPA).
- Author
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S., Sarina, J., Irving, M., Case, L., Minto, N., Bown, S., Bailey, and A., Hall
- Subjects
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LYMPHOBLASTIC leukemia in children , *NUCLEOTIDES , *GENETIC polymorphisms , *PLOIDY , *CANCER , *CANCER cells , *TUMOR suppressor genes - Abstract
Introduction: Allelic imbalance is a common genetic event in many types of malignancy. The recent introduction of high-density SNPA for the concurrent analysis of loss of heterozygosity (LOH) and changes in chromosome copy number (CN) in small amounts of DNA has facilitated a comprehensive, genome-wide analysis of tumour cell populations. This method is of value in malignancies where standard cytogenetic analysis is difficult to perform. Objective: To characterise LOH and CN alterations in leukaemic samples using SNPA. Patients and method: A cohort of 86 patients presenting with childhood ALL within the Northern Region of the UK (Sept 1986-Jan 2005) were analysed using GeneChip® Human Mapping 10K Array (Affymetrix, Ltd.). Good quality of DNA (250ng) was sent to MRC Geneservice (Cambridge) for sample analysis. Results from SNPA analysis were analysed using proprietary software (Affymetrix). The results spreadsheets obtained from MRC contained information about the identity of each SNP and its chromosomal location were exported to Excel spreadsheets for in house analysis. Results: Sixty-nine of the 86 samples (80%) showed one or more significant areas of LOH. Consideration of the CN of the regions affected suggested that this was of 2 types: LOH associated with CN reduction (deletion) and LOH associated with no CN change or copy neutral-LOH (acquired isodisomy, AID). Allelic imbalances have been frequently identified on chromosome 9p, 12p and 6q. Loss of 9p has been associated with tumourigenesis and to be progressive in some cases at relapse. A tumor suppressor gene, p16INK4a is always included in 9p deleted region and has been suggested to be involved in leukaemogenesis. Discussion and conclusion: This study indicated that application of SNPA is very useful to characterize allelic imbalance in childhood ALL. In addition, unlike other whole-genome screening methods, it can readily detect LOH associated with the preservation of the normal CN (AID). [ABSTRACT FROM AUTHOR]
- Published
- 2008