TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms.
Previously we described joining of DNA in the beta T cell receptor gene to DNA of an uncharacterized locus in a t(7;9)(q34;q34.3) chromosomal translocation from a case of human T lymphoblastic leukemia (T-ALL). We now show that the locus on chromosome 9 contains a gene highly homologous to the Drosophila gene Notch. Transcripts of the human gene, for which we propose the name TAN-1, and its murine counterpart are present in many normal human fetal and adult mouse tissues, but are most abundant in lymphoid tissues. In t(7;9)(q34;q34.3) translocations from three cases of T-ALL, the breakpoints occur within 100 bp of an intron in TAN-1, resulting in truncation of TAN-1 transcripts. These observations suggest that TAN-1 may be important for normal lymphocyte function and that alteration of TAN-1 may play a role in the pathogenesis of some T cell neoplasms.
Ellisen
L W
LW
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Bird
J
J
West
D C
DC
Soreng
A L
AL
Reynolds
T C
TC
Smith
S D
SD
Sklar
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D002897:Chromosomes, Human, Pair 7; D002899:Chromosomes, Human, Pair 9; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D051881:Receptor, Notch1; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface; D015183:Restriction Mapping; D014157:Transcription Factors; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D008565:Membrane Proteins; C497761:NOTCH1 protein, human; C497762:Notch1 protein, mouse; D009841:Oligonucleotides; D012333:RNA, Messenger; D051881:Receptor, Notch1; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D004247:DNA