Document Detail


Thiopurine methyltransferase pharmacogenetics. Cloning of human liver cDNA and a processed pseudogene on human chromosome 18q21.1.
MedLine Citation:
PMID:  7628307     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Thiopurine methyltransferase (TPMT) is a genetically polymorphic enzyme that catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine. This genetic polymorphism is an important factor responsible for individual variation in thiopurine drug response. A cDNA for TPMT has been cloned from T84 human colon carcinoma cells. Northern blot analysis of multiple human tissues was performed with the T84 human colon carcinoma TPMT cDNA open reading frame (ORF) as a probe as one step toward understanding the molecular basis for the TPMT genetic polymorphism. Three mRNA species (approximately 1.4, 2.0, and 3.6 kb in length) were present in all tissues studied, including liver. However, none of these mRNAs matched the length of the 2.7 kb T84 TPMT cDNA. Therefore, it was important to clone a TPMT cDNA from a human drug-metabolizing organ such as the liver to determine whether its sequence matched that of the cDNA cloned from the T84 cell line. A human liver cDNA library was screened with the T84 TPMT cDNA ORF as a probe, and a 1.8 kb cDNA was isolated with a coding region sequence identical to that of the T84 TPMT cDNA. The TPMT cDNA ORF was then used to screen a human lymphocytes genomic DNA library in an attempt to clone the TPMT gene(s) in humans. Three intronless clones were isolated with identical ORF sequences that were 96% identical to that of the TPMT cDNA, but which contained multiple nucleotide substitutions and one deletion. The 3'- and 5'-flanking regions of one of the genomic DNA clones were sequenced.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
D Lee; C Szumlanski; J Houtman; R Honchel; K Rojas; J Overhauser; E D Wieben; R M Weinshilboum
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  23     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  1995 Mar 
Date Detail:
Created Date:  1995-09-07     Completed Date:  1995-09-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  398-405     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Mayo Medical School, Rochester, MN 55905-0001, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/U11424;  U12387
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Blotting, Northern
Chromosome Mapping
Chromosomes, Human, Pair 18*
Cloning, Molecular
DNA, Complementary / genetics*
Humans
Liver / metabolism*
Methyltransferases / genetics*
Molecular Sequence Data
Polymorphism, Genetic*
Pseudogenes*
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
GM 28157/GM/NIGMS NIH HHS; GM 35720/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Complementary; EC 2.1.1.-/Methyltransferases; EC 2.1.1.67/thiopurine methyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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