Detailed genome characterization reveals extensive RAG-mediated rearrangements in adult acute lymphoblastic leukemia subgroups

ABSTRACT: Acute lymphoblastic leukemia (ALL) is characterized by the accumulation of somatic genetic alterations in B- or T-lymphoid precursor cells eventually resulting in overt leukemia. We characterized somatic events associated with leukemic transformation by detailed genome-wide copy number analyses of 53 adult B-cell acute lymphoblastic leukemia (B-ALL) and, 20 adult T-cell ALL (T-ALL) cases by comparing to matched control remission specimens. Contrary the paediatric counterpart, adult ALL is scarcely researched in terms of genetic events. We initiated this study to examine whether there are differences in genetic events between paediatric and adult ALL and to observer whether these genetic lesions are driven by aberrant RAG activity. This submission of 53 adult B-ALL and 20 adult T-ALL, with 73 matched control remission material, characterized on the Affymetrix GeneChip Genome-Wide Human SNP 6.0 serves as a repository for multiple studies examining the leukemogenic mechanisms underlying overt ALL establishment. The Affymetrix GeneChip Genome-Wide Human SNP 6.0 was utilized due to its capability to detect copy number variations (CNVs) with high resolution in conjunction to determining genotypes. After informed consent, bone marrow aspirates or peripheral blood samples of a representative cohort of 73 adult ALL patients were collected. Eligible patients had a diagnosis of primary ALL confirmed by cytological examination and immunophenotyping of blood and bone marrow. The majority of these cases were treated following the HOVON (Dutch-Belgian Hematology-Oncology Co-operative group) protocols (http://www.hovon.nl). All studies were approved through the institutional ethics review board and all patients provided written informed consent in accordance to the declaration of Helsinki.
Complementary expression profiling data from the same study have also been deposited at ArrayExpress, under accession number E-MTAB-5035 ( http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-5035/ ). A supplementary file 'DNA_RNA_link_numbers.xlsx' is also provided allowing DNA samples in this submission to be mapped against equivalent RNA sample in E-MTAB-5035.

ORGANISM(S): Homo sapiens

SUBMITTER: Mathijs Sanders 

PROVIDER: E-MTAB-5036 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress