Ann Lab Med.  2012 Nov;32(6):445-449.

Additional Genomic Aberrations Identified by Single Nucleotide Polymorphism Array-Based Karyotyping in an Acute Myeloid Leukemia Case with Isolated del(20q) Abnormality

• Hahm C
• Mun YC
• Seong CM
• Chung WS
• Huh J

Abstract

Prognosis is known to be better in cases with isolated chromosomal abnormalities than in those with complex karyotypes. Accordingly, del(20q) as an isolated abnormality must be distinguished from cases in which it is associated with other chromosomal rearrangements for a better stratification of prognosis. We report a case of an isolated del(20q) abnormality with additional genomic aberrations identified using whole-genome single nucleotide polymorphism array (SNP-A)-based karyotyping. A 39-yr-old man was diagnosed with AML without maturation. Metaphase cytogenetic analysis (MC) revealed del(20)(q11.2) as the isolated abnormality in 100% of metaphase cells analyzed, and FISH analysis using D20S108 confirmed the 20q deletion in 99% of interphase cells. Using FISH, other rearrangements such as BCR/ABL1, RUNX1/RUNX1T1, PML/RARA, CBFB/MYH11, and MLL were found to be negative. SNP-A identified an additional copy neutral loss of heterozygosity (CN-LOH) in the 11q13.1-q25 region. Furthermore, SNP-A allowed for a more precise definition of the breakpoints of the 20q deletion (20q11.22-q13.31). Unexpectedly, the terminal regions showed gain on chromosome 20q. The patient did not achieve complete remission; 8 months later, he died from complications of leukemic cell infiltrations into the central nervous system. This study suggests that a presumably isolated chromosomal abnormality by MC may have additional genomic aberrations, including CN-LOH, which could be associated with a poor prognosis. SNP-A-based karyotyping may be helpful for distinguishing true isolated cases from cases in combination with additional genomic aberrations not detected by MC.

Keyword

Deletion; Chromosome 20; Isolated; AML; Cytogenetics; Single nucleotide polymorphism; Array

MeSH Terms

Adult
Antineoplastic Agents/therapeutic use
Chromosome Deletion
*Chromosomes, Human, Pair 20
Cytogenetic Analysis
Humans
Karyotyping
Leukemia, Myeloid, Acute/*diagnosis/drug therapy/genetics
Loss of Heterozygosity
Male
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
Antineoplastic Agents

Figure

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  Fig. 1 G-banded karyotype showing 46,XY,del(20)(q11.2) (arrow).

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  Fig. 2 SNP array-based karyotyping using genome-wide Human SNP Array 6.0. Signals at the top of each panel represent genotyping calls or the frequency of A and B alleles. The lower panel represents copy number status (CN=1, copy number 1; CN=2, copy number 2; and CN=3, copy number 3). (A) A decrease copy number of 20q11.22-q13.31 (32,253,686-55,192,062) (solid line) and an increased copy number of 20q13.31-q13.33 (55,192,062-59,271,669) (dotted line). (B) Copy neutral loss of heterozygosity (CN-LOH) of 11q13.1-q25. Allele difference values were plotted for consecutive SNP markers along chromosome 11 (solid line). Three genotypes (AA, AB, and BB) were observed along the short arm of chromosome 11, suggesting a normal pattern. In contrast, from band q13.1 to the telomere, a loss of heterozygosity (AA and BB) was observed without copy number change, suggesting the presence of CN-LOH (dotted line).

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