[1331] Comparison of Array Comparative Genomic Hybridization (CGH) to FISH and Cytogenetics in Prognostic Evaluation of CLL

C Giudice, AS Chang, D Chang, TS Barry, MK Hibbard, S Chen, R Chen, DP O'Malley. Clarient Inc., Aliso Viejo, CA

Background: Chronic lymphocytic leukemia (CLL) is a common hematologic neoplasm. Evaluation of prognosis in CLL is based on genetic findings and the most commonly used studies are cytogenetics and targeted fluorescence in situ hybridization (FISH). High resolution array comparative genomic hybridization (aCGH) is a relatively new and robust method of evaluating chromosomal alterations. We compared aCGH with cytogenetics and FISH in detecting genetic alterations in newly-diagnosed CLL cases.
Design: aCGH testing was performed on 55 cases of CLL in addition to a panel of FISH probes (ATM on 11q22, trisomy 12, 13q14, p53 on 17p13 using a standard cutoff for positivity of 10%). These were compared to a control group of 100 CLL with cytogenetic and FISH results. The frequency of abnormalities was compared between the groups and discordant results between methodologies were compared.
Results: In the control group (n=100), the mean age was 71 (52-86) with a male to female ratio of 1.6:1. Genetic abnormalities were detected by cytogenetics in 19% (19/100) of cases as compared to FISH which detected abnormalities in 66% (66/100) of cases (Table 1). An additional group of 55 CLL cases [male to female ratio of 2.2:1 and a mean age of 71 (52-90)] was analyzed by both aCGH and FISH. This additional group of CLL cases showed a similar frequency of genetic abnormalities by FISH (60%; 27/45). In contrast to FISH, aCGH detected genetic abnormalities in 82% (45/55) of CLL cases.

Table 1. Frequency of genetic abnormalities in CLL
CGHFISHCYTOGENETICS
SUBSET I (n=55)82% (45/55)60% (27/45)21% (3/14)
SUBSET II (n=100)N/A66% (66/100)19% (19/100)
TOTAL (n=155)82% (45/55)64% (93/145)19% (22/114)


aCGH identified genetic abnormalities not detected by FISH studies in 16% (7/45) of cases whereas FISH identified abnormalities not detected by aCGH in only 7% (3/45) of cases. Rare recurring genetic alterations were detected by aCGH, which would not have been detected by a standard FISH panel, and included losses in 6q, 8p, 10q, 14q32, and 18q, and gains in 10q.
Conclusions: Cytogenetics is often performed in CLL, but is of limited benefit as CLL cells are often grow poorly and the low rate of detecting common genetic alterations. Our findings suggest aCGH is an effective and robust technique for evaluating recurring genetic abnormalities and is better than cytogenetics and standard FISH in detecting common genetic abnormalities in CLL.
Category: Hematopathology

Monday, March 22, 2010 1:00 PM

Poster Session II # 154, Monday Afternoon

 

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