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Evaluation of chronic lymphocytic leukemia by BAC-based microarray analysis.

Schultz RA, Delioukina M, Gaal K, Bedell V, Smith DD, Forman SJ, McDaniel LD, Ballif BC, Shaffer LG, Slovak ML - Mol Cytogenet (2011)

Bottom Line: For most cases, aCGH was able to detect abnormalities present in as few as 10% of cells.Although changes in ploidy are not easily discernable by aCGH, results for two cases illustrate the detection of additional copy gains and losses present within a mosaic tetraploid cell population.Our results illustrate the successful evaluation of CLL using a microarray optimized for the interrogation of inherited disorders and the identification of alterations with possible relevance to CLL susceptibility.

View Article: PubMed Central - HTML - PubMed

Affiliation: Signature Genomics, 2820 N, Astor St,, Spokane, WA, 99207, USA. lisa.shaffer@perkinelmer.com.

ABSTRACT

Background: Chronic lymphocytic leukemia (CLL) is a highly variable disease with life expectancies ranging from months to decades. Cytogenetic findings play an integral role in defining the prognostic significance and treatment for individual patients.

Results: We have evaluated 25 clinical cases from a tertiary cancer center that have an established diagnosis of CLL and for which there was prior cytogenetic and/or fluorescence in situ hybridization (FISH) data. We performed microarray-based comparative genomic hybridization (aCGH) using a bacterial artificial chromosome (BAC)-based microarray designed for the detection of known constitutional genetic syndromes. In 15 of the 25 cases, aCGH detected all copy number imbalances identified by prior cytogenetic and/or FISH studies. For the majority of those not detected, the aberrations were present at low levels of mosaicism. Furthermore, for 15 of the 25 cases, additional abnormalities were detected. Four of those cases had deletions that mapped to intervals implicated in inherited predisposition to CLL. For most cases, aCGH was able to detect abnormalities present in as few as 10% of cells. Although changes in ploidy are not easily discernable by aCGH, results for two cases illustrate the detection of additional copy gains and losses present within a mosaic tetraploid cell population.

Conclusions: Our results illustrate the successful evaluation of CLL using a microarray optimized for the interrogation of inherited disorders and the identification of alterations with possible relevance to CLL susceptibility.

No MeSH data available.


Related in: MedlinePlus

Microarray characterization of a der(6)del(6)(q15q21)inv(6)(p21.3q23) in case 2. In addition to a del(6)(q15q21) (arrow), single-copy losses were identified at each of the inversion breakpoints. Probes are arranged as in Figure 1A.
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Figure 2: Microarray characterization of a der(6)del(6)(q15q21)inv(6)(p21.3q23) in case 2. In addition to a del(6)(q15q21) (arrow), single-copy losses were identified at each of the inversion breakpoints. Probes are arranged as in Figure 1A.

Mentions: In 15 of 25 (60%) cases, microarray analysis revealed additional complexity. For example, case 2 had both a der(3) and der(6) recognized by chromosome analysis, each of which was associated with an inversion event [der(3)del(3)(p13p21)inv(3)(p21p24), and der(6)del(6)(q15q21)inv(6)(p21.3q23]. The microarray results for chromosome 6 are shown in Figure 2. In addition to detection of the deletion, copy loss was identified at each of the inversion breakpoints. Gains at 1pter, 13qter and 20qter were also noted, as well as a terminal loss at 14q including the IGH locus. FISH analysis detected a 13q14 deletion in 78.5% of cells, and microarray analysis identified a deletion at 13q14.3; however, BAC clone coverage in the region is poor (Figure 3A, 3B). In case 15, microarray analysis detected an ATM deletion, the sole abnormality identified by both chromosomes and FISH.


Evaluation of chronic lymphocytic leukemia by BAC-based microarray analysis.

Schultz RA, Delioukina M, Gaal K, Bedell V, Smith DD, Forman SJ, McDaniel LD, Ballif BC, Shaffer LG, Slovak ML - Mol Cytogenet (2011)

Microarray characterization of a der(6)del(6)(q15q21)inv(6)(p21.3q23) in case 2. In addition to a del(6)(q15q21) (arrow), single-copy losses were identified at each of the inversion breakpoints. Probes are arranged as in Figure 1A.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3045370&req=5

Figure 2: Microarray characterization of a der(6)del(6)(q15q21)inv(6)(p21.3q23) in case 2. In addition to a del(6)(q15q21) (arrow), single-copy losses were identified at each of the inversion breakpoints. Probes are arranged as in Figure 1A.
Mentions: In 15 of 25 (60%) cases, microarray analysis revealed additional complexity. For example, case 2 had both a der(3) and der(6) recognized by chromosome analysis, each of which was associated with an inversion event [der(3)del(3)(p13p21)inv(3)(p21p24), and der(6)del(6)(q15q21)inv(6)(p21.3q23]. The microarray results for chromosome 6 are shown in Figure 2. In addition to detection of the deletion, copy loss was identified at each of the inversion breakpoints. Gains at 1pter, 13qter and 20qter were also noted, as well as a terminal loss at 14q including the IGH locus. FISH analysis detected a 13q14 deletion in 78.5% of cells, and microarray analysis identified a deletion at 13q14.3; however, BAC clone coverage in the region is poor (Figure 3A, 3B). In case 15, microarray analysis detected an ATM deletion, the sole abnormality identified by both chromosomes and FISH.

Bottom Line: For most cases, aCGH was able to detect abnormalities present in as few as 10% of cells.Although changes in ploidy are not easily discernable by aCGH, results for two cases illustrate the detection of additional copy gains and losses present within a mosaic tetraploid cell population.Our results illustrate the successful evaluation of CLL using a microarray optimized for the interrogation of inherited disorders and the identification of alterations with possible relevance to CLL susceptibility.

View Article: PubMed Central - HTML - PubMed

Affiliation: Signature Genomics, 2820 N, Astor St,, Spokane, WA, 99207, USA. lisa.shaffer@perkinelmer.com.

ABSTRACT

Background: Chronic lymphocytic leukemia (CLL) is a highly variable disease with life expectancies ranging from months to decades. Cytogenetic findings play an integral role in defining the prognostic significance and treatment for individual patients.

Results: We have evaluated 25 clinical cases from a tertiary cancer center that have an established diagnosis of CLL and for which there was prior cytogenetic and/or fluorescence in situ hybridization (FISH) data. We performed microarray-based comparative genomic hybridization (aCGH) using a bacterial artificial chromosome (BAC)-based microarray designed for the detection of known constitutional genetic syndromes. In 15 of the 25 cases, aCGH detected all copy number imbalances identified by prior cytogenetic and/or FISH studies. For the majority of those not detected, the aberrations were present at low levels of mosaicism. Furthermore, for 15 of the 25 cases, additional abnormalities were detected. Four of those cases had deletions that mapped to intervals implicated in inherited predisposition to CLL. For most cases, aCGH was able to detect abnormalities present in as few as 10% of cells. Although changes in ploidy are not easily discernable by aCGH, results for two cases illustrate the detection of additional copy gains and losses present within a mosaic tetraploid cell population.

Conclusions: Our results illustrate the successful evaluation of CLL using a microarray optimized for the interrogation of inherited disorders and the identification of alterations with possible relevance to CLL susceptibility.

No MeSH data available.


Related in: MedlinePlus