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HPRT mutations, TCR gene rearrangements, and HTLV‐1 integration sites define in vivo T‐cell clonal lineages
Author(s) -
Allegretta Mark,
Ardell Stephanie K.,
Sullivan Linda M.,
Jacobson Steven,
Mortreux Franck,
Wattel Eric,
Albertini Richard J.
Publication year - 2005
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20120
Subject(s) - biology , t cell receptor , clone (java method) , mutant , genetics , mutation , in vivo , hypoxanthine guanine phosphoribosyltransferase , lineage (genetic) , gene , gene rearrangement , mutagenesis , microbiology and biotechnology , t cell , immune system
HPRT mutations in vivo in human T‐lymphocytes are useful probes for mechanistic investigations. Molecular analyses of isolated mutants reveal their underlying mutational changes as well as the T‐cell receptor (TCR) gene rearrangements present in the cells in question. The latter provide temporal reference points for other perturbations in the in vivo clones as well as evidence of clonal relationships among mutant isolates. Immunological studies and investigations of genomic instability have benefited from such analyses. A method is presented describing a T‐cell lineage analysis in a patient with HTLV‐1 infection. Lineage reconstruction of an in vivo proliferating HPRT mutant clone allows timing of the integration event to a postthymic differentiated cell prior to the occurrence of HPRT mutations. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.