His-1 and His-2: identification and chromosomal mapping of two commonly rearranged sites of viral integration in a myeloid leukemia.
To identify genes that contribute to myeloid leukemogenesis we have cloned viral integration sites from a CasBrM-MuLV-induced interleukin 3-independent myeloid leukemia cell line. Genomic probes derived from cellular sequences flanking two integrated proviruses were used to screen restriction digests of DNAs from a panel of 52 hematopoietic cell lines, 30 of which were established from CasBrM-MuLV- or MoMuLV-induced mouse leukemias. Probes from one integration site (His-1) defined a region that was rearranged in 3/52 cell lines, and probes from a second integration site (His-2) identified a rearrangement in 2/52 cell lines. Both cases of His-2 rearrangements occurred in concert with viral insertions in the His-1 locus. Genetic mapping of these loci using interspecific backcross analysis assigned the His-1 locus to mouse chromosome 2 and the His-2 locus to mouse chromosome 19. In situ hybridization with a probe from the human homologous region mapped the His-1 locus to human chromosome 2q14-q21. No recombinants were observed between His-2 and Gin-1, a common site of provirus integration in Gross passage A MuLV-induced T-cell leukemias, in 131 backcross animals, suggesting that these loci are tightly linked. The His-1 locus maps to mouse chromosome 2 distinct from any known oncogene or common site of integration but near the proximal breakpoint for a deletion that is observed in over 90% of radiation-induced leukemias.
Department of Biochemistry, St Jude Children's Research Hospital, Memphis, Tennessee 38105.
D S
DS
Askew
C
C
Bartholomew
A M
AM
Buchberg
M B
MB
Valentine
N A
NA
Jenkins
N G
NG
Copeland
J N
JN
Ihle
D000818:Animals; D015139:Blotting, Southern; D002460:Cell Line; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D015342:DNA Probes; D015321:Gene Rearrangement; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009693:Nucleic Acid Hybridization; D012150:Polymorphism, Restriction Fragment Length; D016662:Virus Integration
D015342:DNA Probes