Frequent loss of heterozygosity at the TEL gene locus in acute lymphoblastic leukemia of childhood.
TEL is a new member of the ETS family of transcription factors which is rearranged in a number of hematologic malignancies with translocations involving chromosome band 12p13. In some cases, both TEL alleles are affected, resulting in loss of wild-type TEL function in the leukemic cells. In addition, 5% of children with acute lymphoblastic leukemia (ALL) have 12p12-p13 deletions, suggesting that a tumor suppressor gene resides on 12p. These observations led us to consider whether TEL loss of function may contribute to the pathogenesis of ALL. In this report we show that the TEL gene maps between the polymorphic markers D12S89 and D12S98, and we use these flanking markers to screen paired diagnosis and remission samples from 81 children with ALL for loss of heterozygosity (LOH) at the TEL gene locus. Fifteen percent of informative patients showed TEL LOH which was not evident on cytogenetic analysis. Detailed examination of patients with LOH at this locus showed that the critically deleted region included two candidate tumor suppressor genes: TEL and KIP1, the gene encoding the cyclin-dependent kinase inhibitor p27. These studies show that LOH at the TEL locus is a frequent finding in childhood ALL.
Stegmaier
K
K
Division of Hematology/Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Pendse
S
S
Barker
G F
GF
Bray-Ward
P
P
Ward
D C
DC
Montgomery
K T
KT
Krauter
K S
KS
Reynolds
C
C
Sklar
J
J
Donnelly
M
M
D000293:Adolescent; D000782:Aneuploidy; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002881:Chromosomes, Human, Pair 12 / Q000648:ultrastructure; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D007223:Infant; D008297:Male; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics; D008969:Molecular Sequence Data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D017384:Sequence Deletion; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins; D000097764:ETS Translocation Variant 6 Protein
D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D008869:Microtubule-Associated Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000097764:ETS Translocation Variant 6 Protein