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.