Comparison of Array Comparative Genomic Hybridization (aCGH) to FISH and Cytogenetics in Prognostic Evaluation of CLL.

Chronic lymphocytic leukemia (CLL) is a commonly encountered hematologic neoplasm. Evaluation of prognosis in CLL is strongly based on genetic findings and the most commonly used studies are classical cytogenetics and targeted interphase fluorescence in situ hybridization (FISH). High resolution array comparative genomic hybridization (aCGH) is a relatively new and robust method of evaluating chromosomal alterations over the entire genome. We compared aCGH with routine cytogenetics and FISH in detecting genetic alterations in newly-diagnosed CLL cases.

aCGH testing was performed on 55 cases of CLL in addition to a standard panel of FISH probes (ATM on 11q22, trisomy 12, 13q14, p53 on 17p13 using a standard cutoff for positivity of 10%). These results were compared to a control group of 100 CLL cases upon which routine cytogenetics and FISH were performed. The frequency of detecting abnormalities was compared between the groups and discordant results between methodologies were compared.

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 classical 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).

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.

Classical cytogenetics is often performed in cases of CLL, but is not particularly useful as CLL cells are often difficult to grow in culture and because of the low rate of detecting common genetic alterations. Our findings suggest that aCGH is an effective and robust technique for evaluating recurring genetic abnormalities in CLL and is better than classical cytogenetics and standard FISH in detecting common genetic abnormalities in CLL.

No relevant conflicts of interest to declare.