Chronic lymphocytic leukemia (CLL) is a common hematological malignancy in western countries. However, this disease is very rare in Asian countries. It is not clear whether the mechanisms of development of CLL in Caucasian and Asian are same. To answer this question, we compared genomic abnormalities in Asian and Caucasian CLL using single-nucleotide-polymorphism genomic microarray (SNP-chip). We analyzed 75 cases of Japanese CLL (Binet stage A: 51 cases, B: 8 cases, C: 16 cases, unknown: 3 cases) using 250-k GeneChip from Affymetrix. We compared these results to 56 cases of Caucasian CLL. Asian CLL had 4 common genomic abnormalities: deletion of 13q14.3 (36 cases, 49 %), trisomy 12 (23 cases, 30 %), abnormalities of 11q (9 cases, 13 %: 7 deletions and 2 uniparental disomy), and abnormalities of 17p (5 cases, 8 %: 4 deletions and 1 uniparental disomy). These 4 common genomic abnormalities were also identified in Caucasian CLL cases. Interestingly, in both racial groups, trisomy 12 and deletion of 13q14.3 were mutually exclusive (p = 0.01). Nevertheless, frequency of trisomy 12 was higher in Japanese CLL cases (23/75 cases, 30 %) than in Caucasian cases (4/56 cases; 7 %) while frequency of deletion of 13q14.3 was comparable in Japanese and Caucasian (49 % and 48 %, respectively). Frequency of deletion of 11q23.1 was similar in both racial groups. Notably, not only did all these cases involve deletion of ATM but always also deleted miR 34b and 34c. Furthermore, one case had a homozygous deletion of 11q22.3 involving caspase 1/4/5 and COP1. Interestingly, all except one CLL case with 11q abnormalities had either deletion or acquired uniparental disomy. Both Asian and Caucasian CLL had a commonly deleted region at 13q14.3 involving miR 15-a and 16-1. Interestingly, one case had two distinct deletions in this region; one involved miR 15-a and 16-1; the other involved Rb1. On close inspection, 36 % of cases with deletion of 13q, had a deletion of Rb1, suggesting that Rb1 might be another target of deletion of 13q. In summary, the new findings of this study are: 1) Genomic abnormalities in Asian and Caucasian CLL were comparable except for a higher frequency of trisomy 12 in Asian CLL; 2)Trisomy 12 and 13q deletions were mutually exclusive suggesting that either lesion can substitute for the other and may involve a common cellular pathway; 3)New CLL genomic abnormalities include deletion of miR 34b and 34c, caspase 1/4/5 and COP1 (11q), and Rb1 (13q).

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2147.