Chromosome banding analysis and genomic microarrays are both useful but not equivalent methods for genomic complexity risk stratification in chronic lymphocytic leukemia patients

Abstract

Genome complexity has been associated with poor outcome in patients with chronic lymphocytic leukemia (CLL). Previous cooperative studies established five abnormalities as the cut-off that best predicts an adverse evolution by chromosome banding analysis (CBA) and genomic microarrays (GM). However, data comparing risk stratification by both methods are scarce. Herein, we assessed a cohort of 340 untreated CLL patients highly enriched in cases with complex karyotype (CK, 46.5%) with parallel CBA and GM studies. Abnormalities found by both techniques were compared. Prognostic stratification in three risk groups based on genomic complexity [0-2, 3-4 and ≥5 abnormalities] was also analyzed. No significant differences in the percentage of patients classified into each category were detected, but only a moderate agreement was observed between methods when focusing in individual cases (κ=0.507; p

Chromothripsis in Chronic Lymphocytic Leukemia: A Driving Force of Genome Instability

“…Copy-number states can also be analyzed by array-based comparative genomic hybridization (aCGH) or single nucleotide polymorphism (SNP) arrays. However, for the most accurate detection of cth, it is desirable to use a complex approach that combines sequencing genomic methods with molecular cytogenetics and other complementary methods (24). A conventional karyotyping of metaphases can be useful to identify numerical and structural chromosomal abnormalities.…”

“…The evidence of cth cases described in CLL indicates that this phenomenon is a recurrent event. By exploring larger cohorts of CLL patients, cth was observed with frequencies from 1.2 to 10% (2,3,5,18,21,24,38,39). Although the reported prevalence is relatively small, the analysis of cth-like patterns may be beneficial for clinical decision-making and precision medicine, as cth represents a driving force of genome evolution in CLL (5,16,17,20).…”

“…CLL patients with cth (cth-CLL) were shown to have inferior time to first treatment (24), progression-free survival (3), and overall survival (2,3,18,38). The overall survival of cth-CLL cases was even worse than of cases with TP53 abnormality or del(11q) without cth (2).…”

“…The overall survival of cth-CLL cases was even worse than of cases with TP53 abnormality or del(11q) without cth (2). The majority of cth-CLL cases have unmutated IGHV (3,17,24,38,39). Two studies concluded that cth is more frequent in the IGHV-unmutated group with statistical significance (3,38).…”

“…Two studies concluded that cth is more frequent in the IGHV-unmutated group with statistical significance (3,38). There is also a strong link between the presence of cth and high-risk genomic aberrations like del(11q) and del(17p) (2,3,16,17,19,20,24,39). Some studies reported that cth occurs before the CLL diagnosis indicating that the complex genomic remodeling could be a CLL-initiating event (5,16) or one of the earliest events in the CLL pathogenesis (20).…”