Array CGH analysis at 60kb resolution of CML samples at advanced stage of disease
Grace, Colin, Brazma, Diana, Chanalaris, Anastasios, Howard, Julie, Virgili, Anna, Valgañon, Mikel, Cross, Nick, Apperley, Jane F. and Nacheva, Elisabeth (2007) Array CGH analysis at 60kb resolution of CML samples at advanced stage of disease. Blood, 110, (11), p.860A.
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Official URL: http://abstracts.hematologylibrary.org/cgi/content...
Description/Abstract
In spite of the universal presence of the BCR/ABL1 fusion gene, chronic myelogenous leukemia (CML) shows remarkable clinical and genetic diversity. The consequences of der(9)t(9;22) chromosome deletions, associated with poor survival, as well as the mechanism behind their formation remain unclear, as does our understanding of the molecular events driving the disease evolution. The presence of these deletions fuelled the expectations that cryptic genome-wide aberrations may be accountable for the disease progression. Following a comprehensive BAC aCGH analysis of 48 CML samples (Brazma et al., Genes, Chromosomes & Cancer, 2007 in press) we report high-resolution oligo-nucleotide array study of a further 30 CML accelerated/ blast phase samples. We were unable to confirm the high frequency of particular single BAC imbalances (CNVs), reported both by ourselves and others, possibly due to the manufacturer’s array selection strategy. Never-the-less some of the CNVs and a wealth of new imbalances were obtained at 60kb resolution. It was possible to build a precise map of the amplicon affecting the sequences flanking the 3' ABL1 breakpoint site, which include the LAMC3 and NUP214 genes. The presence of this amplicon was associated with therapy resistance. When assessed, at a resolution of 60 kb, the deletions of the regions flanking the ABL1/BCR breakpoint showed novel features:
1. the genome loss affects preferentially both flanking sites as seen in 5 of the 6 ‘deleted’ samples and
2. the 120kb deletion identified is the smallest recorded so far.
Most of the major cytogenetic features of the samples were confirmed and a number of cryptic genome imbalances were detected, from 120kb to 10Mb in size, involving regions rich in genes, some already implicated in the pathogenesis of CML. Finally, recurrent micro aberrations of several adjacent oligo-nucleotides affecting non-coding sequences were detected in as many as 2/3 of the samples.
| Item Type: | Article |
|---|---|
| Additional Information: | ASH Annual Meeting Abstracts 2007: abstract 2927 |
| ISSN: | 0006-4971 (print) |
| Related URLs: | http://abstracts.hematologylib...10/11/2927 |
| Subjects: | R Medicine > RB Pathology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) Q Science > QH Natural history > QH426 Genetics |
| Divisions: | University Structure - Pre August 2011 > School of Medicine |
| ePrint ID: | 60596 |
| URI: | http://eprints.soton.ac.uk/id/eprint/60596 |
| Deposited On: | 07 Nov 2008 |
| Last Modified: | 01 Jun 2011 03:45 |
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