Molecular characterization of 12p abnormalities in hematologic malignancies: deletion of KIP1, rearrangement of TEL, and amplification of CCND2.
Twenty patients with hematologic malignancies with 12p abnormalities were investigated by fluorescence in situ hybridization (FISH) using probes mapped to specific regions in 12p. The initial analysis using the YAC 964c10 (D12S736) revealed that all four cases with cytogenetically identified del(12p) had lost one copy of this YAC and that submicroscopic deletions had occurred in 10 of the 16 neoplasms with other 12p abnormalities, ie, translocations, additions, and insertions. The deletions were partially mapped with cosmids localized to subregions of 12p. One copy of the gene for p27kip1 (KIP1), involved in cell cycle entrance, was found to be lost in all cases in which deletions could be detected by other probes and in one case with a translocation as the only detectable change. This implicates KIP1 as a possible tumor suppressor gene affected by del(12p). Four translocations with no apparent concomitant deletions were detected. All four breakpoints resulted in a split D12S736 signal. In two of these cases, we showed that TEL was disrupted as a result of a t(5;12)(q32-33;p12) and a t(12;22)(p12;q12), respectively. Two lymphoid neoplasm--one non-Hodgkin's lymphoma and one Burkitt's lymphoma--with 12p amplifications were detected. In both cases cyclin D2 (CCND2) was within the amplified region. Thus, cytogenetic abnormalities of 12p in hematologic malignancies result in at least three different molecular changes: deletions of KIP1, amplifications of CCND2, and structural rearrangements of TEL.
Department of Clinical Genetics, University Hospital, Lund, Sweden.
M
M
Höglund
B
B
Johansson
J
J
Pedersen-Bjergaard
P
P
Marynen
F
F
Mitelman
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002051:Burkitt Lymphoma / Q000235:genetics / Q000473:pathology; D018797:Cell Cycle Proteins; D002648:Child; D002869:Chromosome Aberrations; D018244:Chromosomes, Artificial, Yeast; D002881:Chromosomes, Human, Pair 12 / Q000648:ultrastructure*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D009857:Oncogenes; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27