Allele-Specific Tumor Spectrum in Pten Knockin Mice

Hui Wang; Matt Karikomi; Shan Naidu; Ravi Rajmohan; Enrico Caserta; Hui Zi Chen; Maysoon Rawahneh; Julie Moffitt; Julie A. Stephens; Soledad A. Fernandez; Michael Weinstein; Danxin Wang; Wolfgang Sadee; Krista La Perle; Paul Stromberg; Thomas J. Rosol; Charis Eng; Michael C. Ostrowsk; Gustavo Leone

doi:10.1073/pnas.0912524107

Allele-Specific Tumor Spectrum in Pten Knockin Mice

Hui Wang, Matt Karikomi, Shan Naidu, Ravi Rajmohan, Enrico Caserta, Hui Zi Chen, Maysoon Rawahneh, Julie Moffitt, Julie A. Stephens, Soledad A. Fernandez, Michael Weinstein, Danxin Wang, Wolfgang Sadee, Krista La Perle, Paul Stromberg, Thomas J. Rosol, Charis Eng, Michael C. Ostrowsk, Gustavo Leone

Research output: Contribution to journal › Article › peer-review

Abstract

Germline mutations in the tumor suppressor gene PTEN (phosphatase and tensin homology deleted on chromosome 10) cause Cowden and Bannayan-Riley- Ruvalcaba (BRR) syndromes, two dominantly inherited disorders characterized by mental retardation, multiple hamartomas, and variable cancer risk. Here, we modeled three sentinel mutant alleles of PTEN identified in patients with Cowden syndrome and show that the nonsense PtenΔ4-5 and missense PtenC124R and PtenG129E alleles lacking lipid phosphatase activity cause similar developmental abnormalities but distinct tumor spectrawith varying severity and age of onset. Allele-specific differences may be accounted for by loss of function for PtenΔ4-5, hypomorphic function for PtenC124R, and gain of function for Pten G129E. These data demonstrate that the variable tumor phenotypes observed in patients with Cowden and BRR syndromes can be attributed to specificmutations in PTEN that alter protein function through distinct mechanisms.

Original language	American English
Journal	ETSU Faculty Works
Volume	107
Issue number	11
DOIs	https://doi.org/10.1073/pnas.0912524107
State	Published - Mar 16 2010
Externally published	Yes

Keywords

cancer genetics
cowden syndrome

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Wang, H., Karikomi, M., Naidu, S., Rajmohan, R., Caserta, E., Chen, H. Z., Rawahneh, M., Moffitt, J., Stephens, J. A., Fernandez, S. A., Weinstein, M., Wang, D., Sadee, W., La Perle, K., Stromberg, P., Rosol, T. J., Eng, C., Ostrowsk, M. C., & Leone, G. (2010). Allele-Specific Tumor Spectrum in Pten Knockin Mice. ETSU Faculty Works, 107(11). https://doi.org/10.1073/pnas.0912524107

@article{cf2014e63336411c9dfd8fcb79f0bb23,

title = "Allele-Specific Tumor Spectrum in Pten Knockin Mice",

abstract = " Germline mutations in the tumor suppressor gene PTEN (phosphatase and tensin homology deleted on chromosome 10) cause Cowden and Bannayan-Riley- Ruvalcaba (BRR) syndromes, two dominantly inherited disorders characterized by mental retardation, multiple hamartomas, and variable cancer risk. Here, we modeled three sentinel mutant alleles of PTEN identified in patients with Cowden syndrome and show that the nonsense PtenΔ4-5 and missense PtenC124R and PtenG129E alleles lacking lipid phosphatase activity cause similar developmental abnormalities but distinct tumor spectrawith varying severity and age of onset. Allele-specific differences may be accounted for by loss of function for PtenΔ4-5, hypomorphic function for PtenC124R, and gain of function for Pten G129E. These data demonstrate that the variable tumor phenotypes observed in patients with Cowden and BRR syndromes can be attributed to specificmutations in PTEN that alter protein function through distinct mechanisms.",

keywords = "cancer genetics, cowden syndrome",

author = "Hui Wang and Matt Karikomi and Shan Naidu and Ravi Rajmohan and Enrico Caserta and Chen, {Hui Zi} and Maysoon Rawahneh and Julie Moffitt and Stephens, {Julie A.} and Fernandez, {Soledad A.} and Michael Weinstein and Danxin Wang and Wolfgang Sadee and {La Perle}, Krista and Paul Stromberg and Rosol, {Thomas J.} and Charis Eng and Ostrowsk, {Michael C.} and Gustavo Leone",

year = "2010",

month = mar,

day = "16",

doi = "10.1073/pnas.0912524107",

language = "American English",

volume = "107",

journal = "ETSU Faculty Works",

issn = "0027-8424",

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TY - JOUR

T1 - Allele-Specific Tumor Spectrum in Pten Knockin Mice

AU - Wang, Hui

AU - Karikomi, Matt

AU - Naidu, Shan

AU - Rajmohan, Ravi

AU - Caserta, Enrico

AU - Chen, Hui Zi

AU - Rawahneh, Maysoon

AU - Moffitt, Julie

AU - Stephens, Julie A.

AU - Fernandez, Soledad A.

AU - Weinstein, Michael

AU - Wang, Danxin

AU - Sadee, Wolfgang

AU - La Perle, Krista

AU - Stromberg, Paul

AU - Rosol, Thomas J.

AU - Eng, Charis

AU - Ostrowsk, Michael C.

AU - Leone, Gustavo

PY - 2010/3/16

Y1 - 2010/3/16

N2 - Germline mutations in the tumor suppressor gene PTEN (phosphatase and tensin homology deleted on chromosome 10) cause Cowden and Bannayan-Riley- Ruvalcaba (BRR) syndromes, two dominantly inherited disorders characterized by mental retardation, multiple hamartomas, and variable cancer risk. Here, we modeled three sentinel mutant alleles of PTEN identified in patients with Cowden syndrome and show that the nonsense PtenΔ4-5 and missense PtenC124R and PtenG129E alleles lacking lipid phosphatase activity cause similar developmental abnormalities but distinct tumor spectrawith varying severity and age of onset. Allele-specific differences may be accounted for by loss of function for PtenΔ4-5, hypomorphic function for PtenC124R, and gain of function for Pten G129E. These data demonstrate that the variable tumor phenotypes observed in patients with Cowden and BRR syndromes can be attributed to specificmutations in PTEN that alter protein function through distinct mechanisms.

AB - Germline mutations in the tumor suppressor gene PTEN (phosphatase and tensin homology deleted on chromosome 10) cause Cowden and Bannayan-Riley- Ruvalcaba (BRR) syndromes, two dominantly inherited disorders characterized by mental retardation, multiple hamartomas, and variable cancer risk. Here, we modeled three sentinel mutant alleles of PTEN identified in patients with Cowden syndrome and show that the nonsense PtenΔ4-5 and missense PtenC124R and PtenG129E alleles lacking lipid phosphatase activity cause similar developmental abnormalities but distinct tumor spectrawith varying severity and age of onset. Allele-specific differences may be accounted for by loss of function for PtenΔ4-5, hypomorphic function for PtenC124R, and gain of function for Pten G129E. These data demonstrate that the variable tumor phenotypes observed in patients with Cowden and BRR syndromes can be attributed to specificmutations in PTEN that alter protein function through distinct mechanisms.

KW - cancer genetics

KW - cowden syndrome

UR - https://dc.etsu.edu/etsu-works/16725

UR - https://doi.org/10.1073/pnas.0912524107

U2 - 10.1073/pnas.0912524107

DO - 10.1073/pnas.0912524107

M3 - Article

SN - 0027-8424

VL - 107

JO - ETSU Faculty Works

JF - ETSU Faculty Works

IS - 11

ER -

Allele-Specific Tumor Spectrum in Pten Knockin Mice

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Keywords

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