Therapy-induced malignant neoplasms in Nf1 mutant mice

Richard C. Chao, Urszula Pyzel, Jane Fridlyand, Yien Ming Kuo, Lewis Teel, Jennifer Haaga, Alexander Borowsky, Andrew Horvai, Scott C. Kogan, Jeannette Bonifas, Bing Huey, Tyler E. Jacks, Donna Albertson, Kevin M. Shannon

Research output: Contribution to journalArticle

Abstract

Therapy-induced cancers are a severe complication of genotoxic therapies. We used heterozygous Nf1 mutant mice as a sensitized genetic background to investigate tumor induction by radiation (RAD) and cyclophosphamide (CY). Mutagen-exposed Nf1+/- mice developed secondary cancers that are common in humans, including myeloid malignancies, sarcomas, and breast cancers. RAD cooperated strongly with heterozygous Nf1 inactivation in tumorigenesis. Most of the solid tumors showed loss of the wild-type Nf1 allele but retained two Trp53 alleles. Comparative genomic hybridization demonstrated distinct patterns of copy number aberrations in sarcomas and breast cancers from Nf1 mutant mice, and tumor cell lines showed deregulated Ras signaling. Nf1 +/- mice provide a tractable model for investigating the pathogenesis of common mutagen-induced cancers and for testing preventive strategies.

Original languageEnglish (US)
Pages (from-to)337-348
Number of pages12
JournalCancer Cell
Volume8
Issue number4
DOIs
StatePublished - Oct 2005

Fingerprint

Neoplasms
Mutagens
Therapeutics
Alleles
Myeloid Sarcoma
Radiation
Breast Neoplasms
Comparative Genomic Hybridization
Tumor Cell Line
Sarcoma
Cyclophosphamide
Carcinogenesis
Genetic Background

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Chao, R. C., Pyzel, U., Fridlyand, J., Kuo, Y. M., Teel, L., Haaga, J., ... Shannon, K. M. (2005). Therapy-induced malignant neoplasms in Nf1 mutant mice. Cancer Cell, 8(4), 337-348. https://doi.org/10.1016/j.ccr.2005.08.011

Therapy-induced malignant neoplasms in Nf1 mutant mice. / Chao, Richard C.; Pyzel, Urszula; Fridlyand, Jane; Kuo, Yien Ming; Teel, Lewis; Haaga, Jennifer; Borowsky, Alexander; Horvai, Andrew; Kogan, Scott C.; Bonifas, Jeannette; Huey, Bing; Jacks, Tyler E.; Albertson, Donna; Shannon, Kevin M.

In: Cancer Cell, Vol. 8, No. 4, 10.2005, p. 337-348.

Research output: Contribution to journalArticle

Chao, RC, Pyzel, U, Fridlyand, J, Kuo, YM, Teel, L, Haaga, J, Borowsky, A, Horvai, A, Kogan, SC, Bonifas, J, Huey, B, Jacks, TE, Albertson, D & Shannon, KM 2005, 'Therapy-induced malignant neoplasms in Nf1 mutant mice', Cancer Cell, vol. 8, no. 4, pp. 337-348. https://doi.org/10.1016/j.ccr.2005.08.011
Chao RC, Pyzel U, Fridlyand J, Kuo YM, Teel L, Haaga J et al. Therapy-induced malignant neoplasms in Nf1 mutant mice. Cancer Cell. 2005 Oct;8(4):337-348. https://doi.org/10.1016/j.ccr.2005.08.011
Chao, Richard C. ; Pyzel, Urszula ; Fridlyand, Jane ; Kuo, Yien Ming ; Teel, Lewis ; Haaga, Jennifer ; Borowsky, Alexander ; Horvai, Andrew ; Kogan, Scott C. ; Bonifas, Jeannette ; Huey, Bing ; Jacks, Tyler E. ; Albertson, Donna ; Shannon, Kevin M. / Therapy-induced malignant neoplasms in Nf1 mutant mice. In: Cancer Cell. 2005 ; Vol. 8, No. 4. pp. 337-348.
@article{32bc968174fc48f58a667816335e8f3f,
title = "Therapy-induced malignant neoplasms in Nf1 mutant mice",
abstract = "Therapy-induced cancers are a severe complication of genotoxic therapies. We used heterozygous Nf1 mutant mice as a sensitized genetic background to investigate tumor induction by radiation (RAD) and cyclophosphamide (CY). Mutagen-exposed Nf1+/- mice developed secondary cancers that are common in humans, including myeloid malignancies, sarcomas, and breast cancers. RAD cooperated strongly with heterozygous Nf1 inactivation in tumorigenesis. Most of the solid tumors showed loss of the wild-type Nf1 allele but retained two Trp53 alleles. Comparative genomic hybridization demonstrated distinct patterns of copy number aberrations in sarcomas and breast cancers from Nf1 mutant mice, and tumor cell lines showed deregulated Ras signaling. Nf1 +/- mice provide a tractable model for investigating the pathogenesis of common mutagen-induced cancers and for testing preventive strategies.",
author = "Chao, {Richard C.} and Urszula Pyzel and Jane Fridlyand and Kuo, {Yien Ming} and Lewis Teel and Jennifer Haaga and Alexander Borowsky and Andrew Horvai and Kogan, {Scott C.} and Jeannette Bonifas and Bing Huey and Jacks, {Tyler E.} and Donna Albertson and Shannon, {Kevin M.}",
year = "2005",
month = "10",
doi = "10.1016/j.ccr.2005.08.011",
language = "English (US)",
volume = "8",
pages = "337--348",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Therapy-induced malignant neoplasms in Nf1 mutant mice

AU - Chao, Richard C.

AU - Pyzel, Urszula

AU - Fridlyand, Jane

AU - Kuo, Yien Ming

AU - Teel, Lewis

AU - Haaga, Jennifer

AU - Borowsky, Alexander

AU - Horvai, Andrew

AU - Kogan, Scott C.

AU - Bonifas, Jeannette

AU - Huey, Bing

AU - Jacks, Tyler E.

AU - Albertson, Donna

AU - Shannon, Kevin M.

PY - 2005/10

Y1 - 2005/10

N2 - Therapy-induced cancers are a severe complication of genotoxic therapies. We used heterozygous Nf1 mutant mice as a sensitized genetic background to investigate tumor induction by radiation (RAD) and cyclophosphamide (CY). Mutagen-exposed Nf1+/- mice developed secondary cancers that are common in humans, including myeloid malignancies, sarcomas, and breast cancers. RAD cooperated strongly with heterozygous Nf1 inactivation in tumorigenesis. Most of the solid tumors showed loss of the wild-type Nf1 allele but retained two Trp53 alleles. Comparative genomic hybridization demonstrated distinct patterns of copy number aberrations in sarcomas and breast cancers from Nf1 mutant mice, and tumor cell lines showed deregulated Ras signaling. Nf1 +/- mice provide a tractable model for investigating the pathogenesis of common mutagen-induced cancers and for testing preventive strategies.

AB - Therapy-induced cancers are a severe complication of genotoxic therapies. We used heterozygous Nf1 mutant mice as a sensitized genetic background to investigate tumor induction by radiation (RAD) and cyclophosphamide (CY). Mutagen-exposed Nf1+/- mice developed secondary cancers that are common in humans, including myeloid malignancies, sarcomas, and breast cancers. RAD cooperated strongly with heterozygous Nf1 inactivation in tumorigenesis. Most of the solid tumors showed loss of the wild-type Nf1 allele but retained two Trp53 alleles. Comparative genomic hybridization demonstrated distinct patterns of copy number aberrations in sarcomas and breast cancers from Nf1 mutant mice, and tumor cell lines showed deregulated Ras signaling. Nf1 +/- mice provide a tractable model for investigating the pathogenesis of common mutagen-induced cancers and for testing preventive strategies.

UR - http://www.scopus.com/inward/record.url?scp=26644470352&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26644470352&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2005.08.011

DO - 10.1016/j.ccr.2005.08.011

M3 - Article

C2 - 16226708

AN - SCOPUS:26644470352

VL - 8

SP - 337

EP - 348

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 4

ER -