Modeling variation in tumors in vivo

James R. Stringer, Jon S. Larson, Jared Fischer, Marlo Medvedovic, Megan N. Hersh, Gregory P. Boivin, Saundra L. Stringer

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Transgenic mice that allow mutant cells to be visualized in situ were used to study variation in tumors. These mice carry the G11 placental alkaline phosphatase (PLAP) transgene, a mutant allele rendered incapable of producing its enzyme product by a frameshift caused by insertion of a tract of G:C base pairs in a coding region. Spontaneous deletion of one G:C base pair from this tract restores gene function, and cells with PLAP activity can be detected histochemically. To study tumors, the G11 PLAP transgene was introduced into the polyoma virus middle T antigen mammary tumor model. Tumors in these mice exhibited up to 300 times more PLAP + cells than normal tissues. PLAP + cells were located throughout each tumor. Many of the PLAP + cells were singlets, but clusters also were common, with one cluster containing >30,000 cells. Comparison of these data to simulations produced by computer models suggested that multiple factors were involved in generating mutant cells in tumors. Although genetic instability appeared to have occurred in most tumors, large clusters were much more common than expected based on instability alone.

Original languageEnglish (US)
Pages (from-to)2408-2413
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number7
DOIs
StatePublished - Feb 15 2005
Externally publishedYes

Fingerprint

Neoplasms
Transgenes
Base Pairing
Polyomavirus
Viral Tumor Antigens
Computer Simulation
Transgenic Mice
placental alkaline phosphatase
Alleles
Breast Neoplasms
Enzymes
Genes

Keywords

  • Instability
  • Microsatellites
  • Mouse
  • Mutation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Stringer, J. R., Larson, J. S., Fischer, J., Medvedovic, M., Hersh, M. N., Boivin, G. P., & Stringer, S. L. (2005). Modeling variation in tumors in vivo. Proceedings of the National Academy of Sciences of the United States of America, 102(7), 2408-2413. https://doi.org/10.1073/pnas.0401340102

Modeling variation in tumors in vivo. / Stringer, James R.; Larson, Jon S.; Fischer, Jared; Medvedovic, Marlo; Hersh, Megan N.; Boivin, Gregory P.; Stringer, Saundra L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 7, 15.02.2005, p. 2408-2413.

Research output: Contribution to journalArticle

Stringer, JR, Larson, JS, Fischer, J, Medvedovic, M, Hersh, MN, Boivin, GP & Stringer, SL 2005, 'Modeling variation in tumors in vivo', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 7, pp. 2408-2413. https://doi.org/10.1073/pnas.0401340102
Stringer, James R. ; Larson, Jon S. ; Fischer, Jared ; Medvedovic, Marlo ; Hersh, Megan N. ; Boivin, Gregory P. ; Stringer, Saundra L. / Modeling variation in tumors in vivo. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 7. pp. 2408-2413.
@article{f29ecf00a6c5413983da3cf7d8522afa,
title = "Modeling variation in tumors in vivo",
abstract = "Transgenic mice that allow mutant cells to be visualized in situ were used to study variation in tumors. These mice carry the G11 placental alkaline phosphatase (PLAP) transgene, a mutant allele rendered incapable of producing its enzyme product by a frameshift caused by insertion of a tract of G:C base pairs in a coding region. Spontaneous deletion of one G:C base pair from this tract restores gene function, and cells with PLAP activity can be detected histochemically. To study tumors, the G11 PLAP transgene was introduced into the polyoma virus middle T antigen mammary tumor model. Tumors in these mice exhibited up to 300 times more PLAP + cells than normal tissues. PLAP + cells were located throughout each tumor. Many of the PLAP + cells were singlets, but clusters also were common, with one cluster containing >30,000 cells. Comparison of these data to simulations produced by computer models suggested that multiple factors were involved in generating mutant cells in tumors. Although genetic instability appeared to have occurred in most tumors, large clusters were much more common than expected based on instability alone.",
keywords = "Instability, Microsatellites, Mouse, Mutation",
author = "Stringer, {James R.} and Larson, {Jon S.} and Jared Fischer and Marlo Medvedovic and Hersh, {Megan N.} and Boivin, {Gregory P.} and Stringer, {Saundra L.}",
year = "2005",
month = "2",
day = "15",
doi = "10.1073/pnas.0401340102",
language = "English (US)",
volume = "102",
pages = "2408--2413",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "7",

}

TY - JOUR

T1 - Modeling variation in tumors in vivo

AU - Stringer, James R.

AU - Larson, Jon S.

AU - Fischer, Jared

AU - Medvedovic, Marlo

AU - Hersh, Megan N.

AU - Boivin, Gregory P.

AU - Stringer, Saundra L.

PY - 2005/2/15

Y1 - 2005/2/15

N2 - Transgenic mice that allow mutant cells to be visualized in situ were used to study variation in tumors. These mice carry the G11 placental alkaline phosphatase (PLAP) transgene, a mutant allele rendered incapable of producing its enzyme product by a frameshift caused by insertion of a tract of G:C base pairs in a coding region. Spontaneous deletion of one G:C base pair from this tract restores gene function, and cells with PLAP activity can be detected histochemically. To study tumors, the G11 PLAP transgene was introduced into the polyoma virus middle T antigen mammary tumor model. Tumors in these mice exhibited up to 300 times more PLAP + cells than normal tissues. PLAP + cells were located throughout each tumor. Many of the PLAP + cells were singlets, but clusters also were common, with one cluster containing >30,000 cells. Comparison of these data to simulations produced by computer models suggested that multiple factors were involved in generating mutant cells in tumors. Although genetic instability appeared to have occurred in most tumors, large clusters were much more common than expected based on instability alone.

AB - Transgenic mice that allow mutant cells to be visualized in situ were used to study variation in tumors. These mice carry the G11 placental alkaline phosphatase (PLAP) transgene, a mutant allele rendered incapable of producing its enzyme product by a frameshift caused by insertion of a tract of G:C base pairs in a coding region. Spontaneous deletion of one G:C base pair from this tract restores gene function, and cells with PLAP activity can be detected histochemically. To study tumors, the G11 PLAP transgene was introduced into the polyoma virus middle T antigen mammary tumor model. Tumors in these mice exhibited up to 300 times more PLAP + cells than normal tissues. PLAP + cells were located throughout each tumor. Many of the PLAP + cells were singlets, but clusters also were common, with one cluster containing >30,000 cells. Comparison of these data to simulations produced by computer models suggested that multiple factors were involved in generating mutant cells in tumors. Although genetic instability appeared to have occurred in most tumors, large clusters were much more common than expected based on instability alone.

KW - Instability

KW - Microsatellites

KW - Mouse

KW - Mutation

UR - http://www.scopus.com/inward/record.url?scp=14044279304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14044279304&partnerID=8YFLogxK

U2 - 10.1073/pnas.0401340102

DO - 10.1073/pnas.0401340102

M3 - Article

C2 - 15695337

AN - SCOPUS:14044279304

VL - 102

SP - 2408

EP - 2413

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 7

ER -