Identification of critical gene regions in chronic lymphocytic leukemia using high-resolution array comparative genomic hybridization

ABSTRACT: With an objective to identify novel copy number alterations (CNAs) critical to CLL pathogenesis, we performed array comparative genomic hybridization (array CGH) on genomic DNA extracted from purified leukemic cells of 51 CLL patients. We used the 1.4 Mb HumArray platform, and analyzed data using a combination of three different statistical algorithms and in full awareness of the copy number variations (CNVs) found in normal populations. Use of reference DNA extracted from matched patient neutrophils in four cases also assisted a more comprehensive interpretation of constitutional versus CLL-specific copy number alterations. A total of 108 clones showed alterations in >10% of the cases. Of these, 25 clones corresponded to known recurrently acquired CNAs for CLL, representing +12 in 8 cases (16%) and del(13)(q14) in 26 cases (51%). For the remaining 83 clones, frequent deletions corresponded to loci within cytobands 17q12 (71% of CLL cases), 9q32 (55%), 8p23 (47%) and 2q21 (33%), and frequent gains corresponded to loci within cytobands 18q22.3 (51%), 20p12 (33%) and 15q13 (31%), most of which have been reported in normal population cohorts. We further analysed associations between CNV status across the 108 frequently affected clones and CD38 expression status. Consistent with previous findings, loss of 13q14 (represented in clone RPI-269F22) and gain of chromosome 12 (clones RP11-64J22, RMC12P001 and RP11-282G15) were associated with low and high CD38 expression, respectively. We also found that loss within the beta-defensin (DEFB) locus at 8p23, and gains across clones CTB-120N12 (17q25) and RP11-118K20 (13q31.1) were associated with the poor prognostic CD38+ subgroup (p<0.05). Further studies are needed to assess biological relevance of genes located within these regions and prognostic outcomes in CLL.

ORGANISM(S): Homo sapiens

PROVIDER: GSE21998 | GEO | 2017/06/14

SECONDARY ACCESSION(S): PRJNA127221

REPOSITORIES: GEO