Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia.

摘要: Background High-resolution genomic microarrays enable simultaneous detection of copy-number aberrations such as the known recurrent in chronic lymphocytic leukemia [del(11q), del(13q), del(17p) and trisomy 12], neutral loss heterozygosity. Moreover, comparison profiles from sequential patients' samples allows clonal evolution. Design Methods We screened 369 patients with newly diagnosed a population-based cohort using 250K single nucleotide polymorphism-arrays. Clonal evolution was evaluated 59 follow-up obtained after 5-9 years. Results At diagnosis, were identified 90% patients; 70% carried alterations, including del(13q) (55%), 12 (10.5%), del(11q) (10%), (4%). Additional detected on chromosomes 2 (1.9%), 4 (1.4%), 8 (1.6%) 14 (1.6%). Thirteen (3.5%) displayed heterozygosity 13q, whom 11 had concurrent homozygous del(13q). Genomic complexity large 13q deletions correlated inferior outcome, while former linked to poor-prognostic aberrations. In study, developed 8/24 (33%) unmutated IGHV, 4/25 (16%) IGHV-mutated treated patients. contrast, untreated mutated IGHV (n=10) did not acquire additional The most common secondary event, 6/12 (50%) all acquired alterations. Interestingly, on, for example, chromosome 6q, 8p, 9p 10q exclusively IGHV. Conclusions Whole-genome screening revealed high frequency leukemia. associated other markers aggressive disease commonly included