Tumor model-specific proviral insertional mutagenesis of the Fos/Jdp2/Batf locus.

Mads Heilskov Rasmussen; Annette Balle Sørensen; D W Morris; J C Dutra; E K Engelhard; C L Wang; J Schmidt; Finn Skou Pedersen

doi:10.1016/j.virol.2005.04.027

Tumor model-specific proviral insertional mutagenesis of the Fos/Jdp2/Batf locus.

Mads Heilskov Rasmussen, Annette Balle Sørensen, D W Morris, J C Dutra, E K Engelhard, C L Wang, J Schmidt, Finn Skou Pedersen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Abstrakt

Udgivelsesdato: 2005-Jul-5

Originalsprog	Engelsk
Tidsskrift	Virology
Vol/bind	337
Udgave nummer	2
Sider (fra-til)	353-64
Antal sider	11
ISSN	0042-6822
DOI	https://doi.org/10.1016/j.virol.2005.04.027
Status	Udgivet - 2005
Udgivet eksternt	Ja

Adgang til dokumentet

10.1016/j.virol.2005.04.027

Citationsformater

@article{f30a311562a14832adf8a4eed61d9978,

title = "Tumor model-specific proviral insertional mutagenesis of the Fos/Jdp2/Batf locus.",

abstract = "Retroviral activation of the AP-1/ATF super family member Jdp2 was recently reported to be a common event in M-MLV-induced T cell lymphoma in p27-null C57x129 mice as compared to wild type-inoculated mice but has not been found important in other models. On the basis of retroviral tag retrieval from 1190 individual Akv- and SL3-3-induced lymphomas, we here report that insertional mutagenesis into the 250-kb Fos/Jdp2/Batf locus is associated with SL3-3 MLV-induced T but not Akv-induced B cell lymphomas of NMRI and SWR mice. Integration pattern and clonality analyses suggest that Jdp2 participates in SL3-3-induced tumorigenesis distinctly as compared to the M-MLV setting. Northern blot analysis showed Jdp2 to be alternatively spliced in various normal tissues as well as MLV-induced lymphomas. Interestingly, in some tumors, proviral insertion seems to activate different mRNA sub-species. Whereas elevated mRNA levels of the Fos gene could not be correlated with provirus presence, in one case, Northern blot analysis as well as quantitative real-time PCR indicated proviral activation of the AP-1 super family member Batf, a gene not previously reported to be a target of insertional mutagenesis. A novel integration cluster between Jdp2 and Batf apparently did not influence the expression level of either gene, underscoring the importance of addressing expression effects to identify target genes of insertion. Altogether, such distinct insertion patterns point to different mechanism of activation of specific proto-oncogenes and are consequently of importance for the understanding of proviral activation mechanisms as well as the specific role of individual oncogenes in tumor development.",

author = "Rasmussen, {Mads Heilskov} and S{\o}rensen, {Annette Balle} and Morris, {D W} and Dutra, {J C} and Engelhard, {E K} and Wang, {C L} and J Schmidt and Pedersen, {Finn Skou}",

year = "2005",

doi = "10.1016/j.virol.2005.04.027",

language = "English",

volume = "337",

pages = "353--64",

journal = "Virology",

issn = "0042-6822",

publisher = "Academic Press",

number = "2",

}

TY - JOUR

T1 - Tumor model-specific proviral insertional mutagenesis of the Fos/Jdp2/Batf locus.

AU - Rasmussen, Mads Heilskov

AU - Sørensen, Annette Balle

AU - Morris, D W

AU - Dutra, J C

AU - Engelhard, E K

AU - Wang, C L

AU - Schmidt, J

AU - Pedersen, Finn Skou

PY - 2005

Y1 - 2005

N2 - Retroviral activation of the AP-1/ATF super family member Jdp2 was recently reported to be a common event in M-MLV-induced T cell lymphoma in p27-null C57x129 mice as compared to wild type-inoculated mice but has not been found important in other models. On the basis of retroviral tag retrieval from 1190 individual Akv- and SL3-3-induced lymphomas, we here report that insertional mutagenesis into the 250-kb Fos/Jdp2/Batf locus is associated with SL3-3 MLV-induced T but not Akv-induced B cell lymphomas of NMRI and SWR mice. Integration pattern and clonality analyses suggest that Jdp2 participates in SL3-3-induced tumorigenesis distinctly as compared to the M-MLV setting. Northern blot analysis showed Jdp2 to be alternatively spliced in various normal tissues as well as MLV-induced lymphomas. Interestingly, in some tumors, proviral insertion seems to activate different mRNA sub-species. Whereas elevated mRNA levels of the Fos gene could not be correlated with provirus presence, in one case, Northern blot analysis as well as quantitative real-time PCR indicated proviral activation of the AP-1 super family member Batf, a gene not previously reported to be a target of insertional mutagenesis. A novel integration cluster between Jdp2 and Batf apparently did not influence the expression level of either gene, underscoring the importance of addressing expression effects to identify target genes of insertion. Altogether, such distinct insertion patterns point to different mechanism of activation of specific proto-oncogenes and are consequently of importance for the understanding of proviral activation mechanisms as well as the specific role of individual oncogenes in tumor development.

AB - Retroviral activation of the AP-1/ATF super family member Jdp2 was recently reported to be a common event in M-MLV-induced T cell lymphoma in p27-null C57x129 mice as compared to wild type-inoculated mice but has not been found important in other models. On the basis of retroviral tag retrieval from 1190 individual Akv- and SL3-3-induced lymphomas, we here report that insertional mutagenesis into the 250-kb Fos/Jdp2/Batf locus is associated with SL3-3 MLV-induced T but not Akv-induced B cell lymphomas of NMRI and SWR mice. Integration pattern and clonality analyses suggest that Jdp2 participates in SL3-3-induced tumorigenesis distinctly as compared to the M-MLV setting. Northern blot analysis showed Jdp2 to be alternatively spliced in various normal tissues as well as MLV-induced lymphomas. Interestingly, in some tumors, proviral insertion seems to activate different mRNA sub-species. Whereas elevated mRNA levels of the Fos gene could not be correlated with provirus presence, in one case, Northern blot analysis as well as quantitative real-time PCR indicated proviral activation of the AP-1 super family member Batf, a gene not previously reported to be a target of insertional mutagenesis. A novel integration cluster between Jdp2 and Batf apparently did not influence the expression level of either gene, underscoring the importance of addressing expression effects to identify target genes of insertion. Altogether, such distinct insertion patterns point to different mechanism of activation of specific proto-oncogenes and are consequently of importance for the understanding of proviral activation mechanisms as well as the specific role of individual oncogenes in tumor development.

U2 - 10.1016/j.virol.2005.04.027

DO - 10.1016/j.virol.2005.04.027

M3 - Journal article

C2 - 15913695

VL - 337

SP - 353

EP - 364

JO - Virology

JF - Virology

SN - 0042-6822

IS - 2

ER -