Complex karyotype with cryptic FUS gene rearrangement and deletion of NR3C1 and VPREB1 genes in childhood B-cell acute lymphoblastic leukemia: A case report.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematopoietic malignancy characterized by overproduction of immature B-lymphoblasts. B-ALL is the most common pediatric tumor and remains the leading cause of mortality in children and adolescents. Molecular and cytogenetic analyses of B-ALL revealed recurrent genetic and structural genomic alterations which are routinely applied for diagnosis, prognosis and choice of treatment regimen. The present case report describes a 4-year-old female diagnosed with B-ALL. GTG-banding at low resolution revealed an abnormal clone with 46,XX,?t(X;19)(q13;q13.3),der(9) besides normal cells. Molecular cytogenetics demonstrated a balanced translocation between chromosomes 16 and 19, and an unbalanced translocation involving chromosomes 5 and 9. A locus-specific probe additionally identified that the FUS gene in 16p11.2 was split and its 5' region was translocated to subband 19q13.33, whereas the 3' region of the FUS gene remained on the derivative chromosome 16. Overall, this complex karyotype included four different chromosomes and five break events. Further analyses, including array-comparative genomic hybridization, additionally revealed biallelic deletion of the tumor suppressor genes CDKN2A/B, and deletion of the NR3C1 and VPREB1 genes. The patient passed away under treatment due to sepsis.

A complex rearrangement involving cryptic deletion of ETV6 and CDKN1B genes in a case of childhood acute lymphoblastic leukemia.

We report on a case of childhood B-cell lineage acute lymphoblastic leukemia (ALL). Conventional cytogenetic analysis at diagnosis showed the karyotype: 47,XY,add(3)(q?),-12,+2mar[4]/46,XY[18]. Fluorescence in situ hybridization (FISH) revealed a complex rearrangement: 47,XY,der(3)(3pter->3q29::12q13->12q24.33::12p13.31->12p13.2::12q24.33->12qter),der(12)(12pter->12p13.31::12p12.3->12q12::3q29->3qter),+del(21)(q?). The derivative chromosome 3 arose likely from multiple events due to clonal evolution. After insertion of the segment of the short arm of the chromosome 12 to the distal part of the long arm of chromosome 12 [ins(12)(q24.33p13.31p13.2)], a translocation occurred between chromosome 3 and derivative chromosome 12. Additional FISH results disclosed two heterozygous deletions flanking the translocated region on both 12p13.2 approximately p12.3 and 12q12 approximately q13.13. The deleted segment on 12p contains several genes, among the tumor suppressor genes ETV6 and CDKN1B, which are frequently involved in 12p abnormalities in childhood ALL. Thus, the present study documents the loss of both ETV6 and CDKN1B genes accompanying the occurrence of a complex rearrangement involving chromosomes 3 and 12 in a case of childhood ALL.