Reference SummaryMonahan KB, Oncogene 2010 Aug 9;():

Title

Somatic p16(INK4a) loss accelerates melanomagenesis.

Authors

Monahan KB; Rozenberg GI; Krishnamurthy J; Johnson SM; Liu W; Bradford MK; Horner J; Depinho RA; Sharpless NE

Journal

Oncogene

Volume

Issue

Year

2010

Pages

Abstract

Loss of p16(INK4a)-RB and ARF-p53 tumor suppressor pathways, as well as activation of RAS-RAF signaling, is seen in a majority of human melanomas. Although heterozygous germline mutations of p16(INK4a) are associated with familial melanoma, most melanomas result from somatic genetic events: often p16(INK4a) loss and N-RAS or B-RAF mutational activation, with a minority possessing alternative genetic alterations such as activating mutations in K-RAS and/or p53 inactivation. To generate a murine model of melanoma featuring some of these somatic genetic events, we engineered a novel conditional p16(INK4a)-null allele and combined this allele with a melanocyte-specific, inducible CRE recombinase strain, a conditional p53-null allele and a loxP-stop-loxP activatable oncogenic K-Ras allele. We found potent synergy between melanocyte-specific activation of K-Ras and loss of p16(INK4a) and/or p53 in melanomagenesis. Mice harboring melanocyte-specific activated K-Ras and loss of p16(INK4a) and/or p53 developed invasive, unpigmented and nonmetastatic melanomas with short latency and high penetrance. In addition, the capacity of these somatic genetic events to rapidly induce melanomas in adult mice suggests that melanocytes remain susceptible to transformation throughout adulthood.Oncogene advance online publication, 9 August 2010; doi:10.1038/onc.2010.314.

Links

J:164588 – Mouse Genome Informatics
20697345 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[not specified]-Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Eye - Uvea - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Eye - Uvea - Melanocyte

0

[not specified]-Cdkn2atm2.1Nesh Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Eye - Uvea - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Eye - Uvea - Melanocyte

0

[not specified]-Cdkn2atm2.1Nesh Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Eye - Uvea - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Eye - Uvea - Melanocyte

0

[not specified]-Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Eye - Uvea - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Eye - Uvea - Melanocyte

0

[not specified]-Cdkn2atm2.1Nesh/+ Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Eye - Uvea - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Eye - Uvea - Melanocyte

0

[not specified]-Cdkn2atm2.1Nesh Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn/+ Eye - Uvea - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Eye - Uvea - Melanocyte

0

[not specified]-Cdkn2atm2.1Nesh/+ Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn/+ Eye - Uvea - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Eye - Uvea - Melanocyte

0

[not specified]-Cdkn2atm2.1Nesh Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Eye - Uvea - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Eye - Uvea - Melanocyte

0

[not specified]-Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Lung tumor
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Lung

7.1

[not specified]-Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Skin - Melanocyte hyperplasia
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

observed

[not specified]-Cdkn2atm2.1Nesh Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Skin - Melanocyte hyperplasia
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

observed

[not specified]-Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Skin - Melanocyte hyperplasia
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

observed

[not specified]-Cdkn2atm2.1Nesh Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Skin - Melanocyte hyperplasia
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

observed

[not specified]-Cdkn2atm2.1Nesh Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Skin - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
  • manual depilation
Skin - Melanocyte

63

[not specified] Skin - Melanocyte melanoma
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
  • manual depilation
Skin - Melanocyte

0

[not specified]-Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Skin - Melanocyte melanoma - amelanotic
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

7.1

[not specified]-Cdkn2atm2.1Nesh Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Skin - Melanocyte melanoma - amelanotic
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

5.3

[not specified]-Cdkn2atm2.1Nesh Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Skin - Melanocyte melanoma - amelanotic
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

73

[not specified]-Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Skin - Melanocyte melanoma - amelanotic
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

45

[not specified]-Cdkn2atm2.1Nesh/+ Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Skin - Melanocyte melanoma - amelanotic
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

100

[not specified]-Cdkn2atm2.1Nesh Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn/+ Skin - Melanocyte melanoma - amelanotic
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

100

[not specified]-Cdkn2atm2.1Nesh/+ Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn/+ Skin - Melanocyte melanoma - amelanotic
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

43

[not specified]-Cdkn2atm2.1Nesh Krastm4Tyj/+ Tg(Tyr-cre/ERT2)13Bos Trp53tm1Brn Skin - Melanocyte melanoma - amelanotic
  • 4-hydroxytamoxifen (4-OHT) (for inducing expression from mutant alleles)
Skin - Melanocyte

100

[not specified]-Cdkn2atm1Rdp Tg(Tyr-HRAS)60Lc Skin - Melanocyte melanoma - amelanotic Skin - Melanocyte

100