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. 2011 Jan 20:4:3.
doi: 10.1186/1755-8166-4-3.

Evidence-based genomic diagnosis characterized chromosomal and cryptic imbalances in 30 elderly patients with myelodysplastic syndrome and acute myeloid leukemia

Renu Bajaj  1 , Fang Xu, Bixia Xiang, Katherine Wilcox, Autumn J Diadamo, Rachana Kumar, Alexandra Pietraszkiewicz, Stephanie Halene, Peining Li
Affiliations

Evidence-based genomic diagnosis characterized chromosomal and cryptic imbalances in 30 elderly patients with myelodysplastic syndrome and acute myeloid leukemia

Renu Bajaj et al. Mol Cytogenet. .

Abstract

Background: To evaluate the clinical validity of genome-wide oligonucleotide array comparative genomic hybridization (aCGH) for detecting somatic abnormalities, we have applied this genomic analysis to 30 cases (13 MDS and 17 AML) with clonal chromosomal abnormalities detected in more than 50% of analyzed metaphase cells.

Results: The aCGH detected all numerical chromosomal gains and losses from the mainline clones and 113 copy number alterations (CNAs) ranging from 0.257 to 102.519 megabases (Mb). Clinically significant recurrent deletions of 5q (involving the RPS14 gene), 12p12.3 (ETV6 gene), 17p13 (TP53 gene), 17q11.2 (NF1 gene) and 20q, double minutes containing the MYC gene and segmental amplification involving the MLL gene were further characterized with defined breakpoints and gene contents. Genomic features of microdeletions at 17q11.2 were confirmed by FISH using targeted BAC clones. The aCGH also defined break points in a derivative chromosome 6, der(6)t(3;6)(q21.3;p22.2), and an isodicentric X chromosome. However, chromosomally observed sideline clonal abnormalities in five cases were not detected by aCGH.

Conclusions: Our data indicated that an integrated cytogenomic analysis will be a better diagnostic scheme to delineate genomic contents of chromosomal and cryptic abnormalities in patients with MDS and AML. An evidence-based approach to interpret somatic genomic findings was proposed.

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Figures

Figure 1
Figure 1
Genome-wide incidence map of abnormal findings from the 30 MDS and AML cases. Complied deletions (red) and duplications (green) from all cases are shown in the top panel and from subgroups based on the major chromosomal abnormalities of 5q deletion (n = 9), 7q deletion (n = 3), trisomy 8 (n = 3), 20q deletion (n = 2), loss of Y chromosome (n = 3) and others (n = 10) are shown in the bottom panel.
Figure 2
Figure 2
Genomic features of chromosomal abnormalities and cryptic alterations. A) Genome and chromosome views and correlated chromosomal rearrangements for case #4 show large deletion in 5q, truncated deletions in 7p, cryptic deletions in 9p23 and 17q11 (arrows), large duplication and deletion in 17q, a loss of a chromosome 18, segmental duplication and deletion in 22q. The 17q12-q21.31 duplication and 17q21.31-q24.1 deletion may be translocated onto the deleted 5q, and the 22q11.21-q12.3 duplication and 22q13.31-qter deletion may be initiated from a 22q/22q translocation. B) Left panel shows a cryptic genomic deletion of 17q11 in case #22 and FISH using probes for the NF1 and RHOT1 genes confirmed the NF1 gene deletion. Middle panel shows a deletion of 17q11.2 including the NF1 and RHOT1 genes in case #5 and a 17q11.2 deletion distal to the NF1 gene in case #13. Right panel shows complex 11q deletion and amplification involving the MLL gene at 11q23.3 in case #1.
Figure 3
Figure 3
Integrated cytogenomic workflow and proposed algorithm for interpreting and reporting clinically significant genomic findings.
See this image and copyright information in PMC

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