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PMID: 3194194 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The first BCR gene intron contains breakpoints in Philadelphia chromosome positive leukemia.

Nucleic acids research ·Vol. 16 ·No. 21 ·1988-11-11 ·Pages 10069-81

Heisterkamp N, Knoppel E, Groffen J

Abstract

The hallmark of chronic myelogenous leukemia (CML) is a translocation between chromosomes 9 and 22 - the Philadelphia (Ph') translocation. The translocation is also found in acute lymphocytic leukemia (ALL) albeit in a lower percentage of patients. The breakpoint on chromosome 22 is located within the BCR gene: in CML, breakpoints are clustered within 5.8 kb of DNA, the major breakpoint cluster region (Mbcr). In ALL, breakpoints have been reported within the Mbcr but also in more 5' regions encompassing the BCR gene. To characterize the latter breakpoints, we have molecularly cloned and mapped the entire gene, which encompasses approximately 130 kb of DNA. Mbcr negative, Ph'-positive ALL breakpoints were not distributed at random within the gene but rather were found exclusively within the 3' half of the first BCR gene intron. In contrast to the Mbcr, which is limited to a region of 5.8 kb, this part of the intron has a size of 35 kb. Translocation breakpoints in this region appear to be specific for ALL, since it was not rearranged in clinically well-defined CML specimens nor in any other tumor DNA samples examined.

MeSH Terms
Base Sequence Chromosome Inversion Chromosomes, Human, Pair 22 Chromosomes, Human, Pair 9 Cosmids Humans Introns Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics Molecular Sequence Data Oncogenes Philadelphia Chromosome Restriction Mapping Translocation, Genetic
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Heisterkamp N
Section of Molecular Genetics, Childrens Hospital of Los Angeles, CA 90027.
Knoppel E
Groffen J
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47 references, click to expand
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/16.21.10069
Published
1988-11-11
Pages
10069-81
Language
English
Region
England
NLM ID
0411011
PMCID
PMC338837
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/16.21.10069 PMC Full Text View journal details
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