In:
Genes, Chromosomes and Cancer, Wiley, Vol. 45, No. 11 ( 2006-11), p. 1041-1049
Abstract:
The majority of translocations that involve the long arms of chromosomes 11 and 17 in acute myeloid leukemia appear identical on the cytogenetic level. Nevertheless, they are diverse on the molecular level. At present, two genes are known in 11q23 and four in 17q12‐25 that generate five distinct fusion genes: MLL ‐ MLLT 6/AF 17 , MLL ‐ LASP 1 , MLL‐ACACA or MLL ‐ SEPT 9/MSF, and ZBTB 16/PLZF‐RARA . We analyzed 14 cases with a t(11;17) by fluorescence in situ hybridization and molecular genetic techniques and determined the molecular characteristics of their fusion genes. We identified six different gene fusions that comprised seven cases with a MLL‐MLLT 6/AF 17 , three with a MLL‐SEPT 9/MSF , and one each with MLL‐LASP 1 , MLL‐ACACA , and ZBTB 16/PLZF‐RARA fusions. In the remaining case, a MLL ‐ SEPT 6/ Xq24 fusion suggested a complex rearrangement. The MLL‐MLLT 6/AF 17 transcripts were extremely heterogeneous and the detection of seven different in‐frame transcript and splice variants enabled us to predict the protein domains relevant for leukemogenesis. The putative MLL‐MLLT6 consensus chimeric protein consists of the AT‐hook DNA‐binding, the methyltransferase, and the CXXC zinc‐finger domains of MLL and the highly conserved octapeptide and the leucine‐zipper dimerization motifs of MLLT6. The MLL‐SEPT 9 transcripts showed a similar high degree of variability. These analyses prove that the diverse types of t(11;17)‐associated fusion genes can be reliably identified and delineated with a proper combination of cytogenetic and molecular genetic techniques. The heterogeneity of transcripts encountered in cases with MLL‐MLLT 6/AF 17 and MLL‐SEPT 9/MSF fusions clearly demonstrates that thorough attention has to be paid to the appropriate selection of primers to cover all these hitherto unrecognized fusion variants. © 2006 Wiley‐Liss, Inc.
Type of Medium:
Online Resource
ISSN:
1045-2257
,
1098-2264
Language:
English
Publisher:
Wiley
Publication Date:
2006
detail.hit.zdb_id:
1018988-9
detail.hit.zdb_id:
1492641-6
SSG:
12
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