Chromosomal instability associated with adverse outcome: a case report of patient with Nijmegen breakage syndrome and rapidly developed T-NHL with complex karyotype

Nijmegen breakage syndrome (NBS) is a rare genetic disorder inherited in an autosomal recessive pattern associated with an increased risk of developing lymphoproliferative disorders, mainly non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). This work presents a patient previously diagnosed with Nijmegen breakage syndrome who rapidly developed T-NHL despite of constant medical supervision. Cytogenetic karyotype and microarray tests revealed complex aberrations, indicating enhanced chromosomal instability. The microarray analyses were performed with the use of a CytoScan HD array. All laboratory procedures were carried out according to the manufacturers' protocols. The study was based on an analysis of scanned data files that was generated with the Chromosome Analysis Suite v 3.3 (ChAS, Thermo Fisher Scientific, Waltham, MA). Furthermore, the copy numbers of altered regions (CNAs) were calculated, and the data were normalized to a reference model (Thermo Fisher Scientific) of baseline reference intensities, NA 33 (hg19/CRCh37). The copy number states (CNS) and their breakpoints were determined with the use of the hidden Markov model (HMM) software package. The threshold levels of log2 ratio ≥0.5 and ≤0.5 were used for the categorization of the altered chromosomal regions as CNV gains and losses, respectively. The obtained data were analyzed based on two different criteria: genome-wide CNVs and leukaemia-associated region/gene-specific CNAs (leukaemia genes_all_20150505; Fullerton Overlap Map_hg19).