<i>HPRT</i> mutations, TCR gene rearrangements, and HTLV‐1 integration sites define in vivo T‐cell clonal lineages

Allegretta, Mark; Ardell, Stephanie; Sullivan, Linda; Jacobson, Steven; Mortreux, Franck; Wattel, Éric; Albertini, Richard J.

doi:10.1002/em.20120

Cited by 4 publications

(1 citation statement)

References 47 publications

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“…In agreement with previous data on the DNA of circulating T-lymphocytes [10], [11], [15], [16], our data clearly show genetic heterogeneity for HPRT in healthy individuals (Fig. 3A).…”

Section: Discussionsupporting

confidence: 93%

Evidence of Genetic Instability in Tumors and Normal Nearby Tissues

Geraci

D'Elia²,

Gaudio³

et al. 2010

PLoS ONE

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BackgroundComprehensive analyses have recently been performed on many human cancer tissues, leading to the identification of a number of mutated genes but providing no information on the variety of mutations present in each of them. This information is of interest to understand the possible origin of gene mutations that cause tumors.Methodology/Principal FindingsWe have analyzed the sequence heterogeneity of the transcripts of the human HPRT and G6PD single copy genes that are not considered tumor markers. Analyses have been performed on different colon cancers and on the nearby histologically normal tissues of two male patients. Several copies of each cDNA, which were produced by cloning the RT-PCR-amplified fragments of the specific mRNA, have been sequenced. Similar analyses have been performed on blood samples of two ostensibly healthy males as reference controls. The sequence heterogeneity of the HPRT and G6PD genes was also determined on DNA from tumor tissues. The employed analytical approach revealed the presence of low-frequency mutations not detectable by other procedures. The results show that genetic heterogeneity is detectable in HPRT and G6PD transcripts in both tumors and nearby healthy tissues of the two studied colon tumors. Similar frequencies of mutations are observed in patient genomic DNA, indicating that mutations have a somatic origin. HPRT transcripts show genetic heterogeneity also in healthy individuals, in agreement with previous results on human T-cells, while G6PD transcript heterogeneity is a characteristic of the patient tissues. Interestingly, data on TP53 show little, if any, heterogeneity in the same tissues.Conclusions/SignificanceThese findings show that genetic heterogeneity is a peculiarity not only of cancer cells but also of the normal tissue where a tumor arises.

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“…In agreement with previous data on the DNA of circulating T-lymphocytes [10], [11], [15], [16], our data clearly show genetic heterogeneity for HPRT in healthy individuals (Fig. 3A).…”

Section: Discussionsupporting

confidence: 93%

Evidence of Genetic Instability in Tumors and Normal Nearby Tissues

Geraci

D'Elia²,

Gaudio³

et al. 2010

PLoS ONE

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Analysis of In Vivo Mutation in the Hprt and Tk Genes of Mouse Lymphocytes

Dobrovolsky¹,

Shaddock²,

Heflich³

2020

Molecular Toxicology Protocols

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Analysis of In Vivo Mutation in the Hprt and Tk Genes of Mouse Lymphocytes

Dobrovolsky

Shaddock

Heflich

2014

Molecular Toxicology Protocols

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Assays measuring mutant frequencies in endogenous reporter genes are used for identifying potentially genotoxic environmental agents and discovering phenotypes prone to genomic instability and diseases, such as cancer. Here, we describe methods for identifying mouse spleen lymphocytes with mutations in the endogenous X-linked hypoxanthine guanine phosphoribosyl transferase (Hprt) gene and the endogenous autosomal thymidine kinase (Tk) gene. The selective clonal expansion of mutant lymphocytes is based upon the phenotypic properties of HPRT- and TK-deficient cells. The same procedure can be utilized for quantifying Hprt mutations in most strains of mice (and, with minor changes, in other mammalian species), while mutations in the Tk gene can be determined only in transgenic mice that are heterozygous for inactivation of this gene. Expanded mutant clones can be further analyzed to classify the types of mutations in the Tk gene (small intragenic mutations vs. large chromosomal mutations) and to determine the nature of intragenic mutation in both the Hprt and Tk genes.

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HPRT mutations, TCR gene rearrangements, and HTLV‐1 integration sites define in vivo T‐cell clonal lineages

Cited by 4 publications

References 47 publications

Evidence of Genetic Instability in Tumors and Normal Nearby Tissues

Evidence of Genetic Instability in Tumors and Normal Nearby Tissues

Analysis of In Vivo Mutation in the Hprt and Tk Genes of Mouse Lymphocytes

Analysis of In Vivo Mutation in the Hprt and Tk Genes of Mouse Lymphocytes

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