Oncogenic ERBB3 Mutations in Human Cancers

Bijay S. Jaiswal; Noelyn M. Kljavin; Eric W. Stawiski; Emily Chan; Chaitali Parikh; Steffen Durinck; Subhra Chaudhuri; Kanan Pujara; Joseph Guillory; Kyle A. Edgar; Vasantharajan Janakiraman; Rolf Peter Scholz; Krista Bowman; Maria Lorenzo; Hong Li; Jiansheng Wu; Wenlin Yuan; Brock A. Peters; Zhengyan Kan; Jeremy Stinson; Michelle Mak; Zora Modrusan; Charles Eigenbrot; Ron Firestein; Howard M. Stern; Krishnaraj Rajalingam; Gabriele Schaefer; Mark A. Merchant; Mark X. Sliwkowski; Frederic J. deSauvage; Somasekar Seshagiri

doi:10.1016/j.ccr.2013.04.012

Oncogenic ERBB3 Mutations in Human Cancers

Bijay S. Jaiswal, Noelyn M. Kljavin, Eric W. Stawiski, Emily Chan, Chaitali Parikh, Steffen Durinck, Subhra Chaudhuri, Kanan Pujara, Joseph Guillory, Kyle A. Edgar, Vasantharajan Janakiraman, Rolf Peter Scholz, Krista Bowman, Maria Lorenzo, Hong Li, Jiansheng Wu, Wenlin Yuan, Brock A. Peters, Zhengyan Kan, Jeremy StinsonMichelle Mak, Zora Modrusan, Charles Eigenbrot, Ron Firestein, Howard M. Stern, Krishnaraj Rajalingam, Gabriele Schaefer, Mark A. Merchant, Mark X. Sliwkowski, Frederic J. deSauvage, Somasekar Seshagiri

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

273 Citations (Scopus)

Abstract

The human epidermal growth factor receptor (HER) family of tyrosine kinases is deregulated in multiple cancers either through amplification, overexpression, or mutation. ERBB3/HER3, the only member with an impaired kinase domain, although amplified or overexpressed in some cancers, has not been reported to carry oncogenic mutations. Here, we report the identification of ERBB3 somatic mutations in ~11% of colon and gastric cancers. We found that the ERBB3 mutants transformed colonic and breast epithelial cells in a ligand-independent manner. However, the mutant ERBB3 oncogenic activity was dependent on kinase-active ERBB2. Furthermore, we found that anti-ERBB antibodies and small molecule inhibitors effectively blocked mutant ERBB3-mediated oncogenic signaling and disease progression invivo.

Original language	English
Pages (from-to)	603-617
Number of pages	15
Journal	Cancer Cell
Volume	23
Issue number	5
DOIs	https://doi.org/10.1016/j.ccr.2013.04.012
Publication status	Published - 13 May 2013
Externally published	Yes

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10.1016/j.ccr.2013.04.012

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Jaiswal, B. S., Kljavin, N. M., Stawiski, E. W., Chan, E., Parikh, C., Durinck, S., Chaudhuri, S., Pujara, K., Guillory, J., Edgar, K. A., Janakiraman, V., Scholz, R. P., Bowman, K., Lorenzo, M., Li, H., Wu, J., Yuan, W., Peters, B. A., Kan, Z., ... Seshagiri, S. (2013). Oncogenic ERBB3 Mutations in Human Cancers. Cancer Cell, 23(5), 603-617. https://doi.org/10.1016/j.ccr.2013.04.012

Jaiswal, Bijay S. ; Kljavin, Noelyn M. ; Stawiski, Eric W. ; Chan, Emily ; Parikh, Chaitali ; Durinck, Steffen ; Chaudhuri, Subhra ; Pujara, Kanan ; Guillory, Joseph ; Edgar, Kyle A. ; Janakiraman, Vasantharajan ; Scholz, Rolf Peter ; Bowman, Krista ; Lorenzo, Maria ; Li, Hong ; Wu, Jiansheng ; Yuan, Wenlin ; Peters, Brock A. ; Kan, Zhengyan ; Stinson, Jeremy ; Mak, Michelle ; Modrusan, Zora ; Eigenbrot, Charles ; Firestein, Ron ; Stern, Howard M. ; Rajalingam, Krishnaraj ; Schaefer, Gabriele ; Merchant, Mark A. ; Sliwkowski, Mark X. ; deSauvage, Frederic J. ; Seshagiri, Somasekar. / Oncogenic ERBB3 Mutations in Human Cancers. In: Cancer Cell. 2013 ; Vol. 23, No. 5. pp. 603-617.

@article{0b42609cd0e64024bac129323297616b,

title = "Oncogenic ERBB3 Mutations in Human Cancers",

abstract = "The human epidermal growth factor receptor (HER) family of tyrosine kinases is deregulated in multiple cancers either through amplification, overexpression, or mutation. ERBB3/HER3, the only member with an impaired kinase domain, although amplified or overexpressed in some cancers, has not been reported to carry oncogenic mutations. Here, we report the identification of ERBB3 somatic mutations in ~11% of colon and gastric cancers. We found that the ERBB3 mutants transformed colonic and breast epithelial cells in a ligand-independent manner. However, the mutant ERBB3 oncogenic activity was dependent on kinase-active ERBB2. Furthermore, we found that anti-ERBB antibodies and small molecule inhibitors effectively blocked mutant ERBB3-mediated oncogenic signaling and disease progression invivo. ",

author = "Jaiswal, {Bijay S.} and Kljavin, {Noelyn M.} and Stawiski, {Eric W.} and Emily Chan and Chaitali Parikh and Steffen Durinck and Subhra Chaudhuri and Kanan Pujara and Joseph Guillory and Edgar, {Kyle A.} and Vasantharajan Janakiraman and Scholz, {Rolf Peter} and Krista Bowman and Maria Lorenzo and Hong Li and Jiansheng Wu and Wenlin Yuan and Peters, {Brock A.} and Zhengyan Kan and Jeremy Stinson and Michelle Mak and Zora Modrusan and Charles Eigenbrot and Ron Firestein and Stern, {Howard M.} and Krishnaraj Rajalingam and Gabriele Schaefer and Merchant, {Mark A.} and Sliwkowski, {Mark X.} and deSauvage, {Frederic J.} and Somasekar Seshagiri",

year = "2013",

month = may,

day = "13",

doi = "10.1016/j.ccr.2013.04.012",

language = "English",

volume = "23",

pages = "603--617",

journal = "Cancer Cell",

issn = "1535-6108",

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Jaiswal, BS, Kljavin, NM, Stawiski, EW, Chan, E, Parikh, C, Durinck, S, Chaudhuri, S, Pujara, K, Guillory, J, Edgar, KA, Janakiraman, V, Scholz, RP, Bowman, K, Lorenzo, M, Li, H, Wu, J, Yuan, W, Peters, BA, Kan, Z, Stinson, J, Mak, M, Modrusan, Z, Eigenbrot, C, Firestein, R, Stern, HM, Rajalingam, K, Schaefer, G, Merchant, MA, Sliwkowski, MX, deSauvage, FJ & Seshagiri, S 2013, 'Oncogenic ERBB3 Mutations in Human Cancers', Cancer Cell, vol. 23, no. 5, pp. 603-617. https://doi.org/10.1016/j.ccr.2013.04.012

Oncogenic ERBB3 Mutations in Human Cancers. / Jaiswal, Bijay S.; Kljavin, Noelyn M.; Stawiski, Eric W.; Chan, Emily; Parikh, Chaitali; Durinck, Steffen; Chaudhuri, Subhra; Pujara, Kanan; Guillory, Joseph; Edgar, Kyle A.; Janakiraman, Vasantharajan; Scholz, Rolf Peter; Bowman, Krista; Lorenzo, Maria; Li, Hong; Wu, Jiansheng; Yuan, Wenlin; Peters, Brock A.; Kan, Zhengyan; Stinson, Jeremy; Mak, Michelle; Modrusan, Zora; Eigenbrot, Charles; Firestein, Ron; Stern, Howard M.; Rajalingam, Krishnaraj; Schaefer, Gabriele; Merchant, Mark A.; Sliwkowski, Mark X.; deSauvage, Frederic J.; Seshagiri, Somasekar.

In: Cancer Cell, Vol. 23, No. 5, 13.05.2013, p. 603-617.

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

TY - JOUR

T1 - Oncogenic ERBB3 Mutations in Human Cancers

AU - Jaiswal, Bijay S.

AU - Kljavin, Noelyn M.

AU - Stawiski, Eric W.

AU - Chan, Emily

AU - Parikh, Chaitali

AU - Durinck, Steffen

AU - Chaudhuri, Subhra

AU - Pujara, Kanan

AU - Guillory, Joseph

AU - Edgar, Kyle A.

AU - Janakiraman, Vasantharajan

AU - Scholz, Rolf Peter

AU - Bowman, Krista

AU - Lorenzo, Maria

AU - Li, Hong

AU - Wu, Jiansheng

AU - Yuan, Wenlin

AU - Peters, Brock A.

AU - Kan, Zhengyan

AU - Stinson, Jeremy

AU - Mak, Michelle

AU - Modrusan, Zora

AU - Eigenbrot, Charles

AU - Firestein, Ron

AU - Stern, Howard M.

AU - Rajalingam, Krishnaraj

AU - Schaefer, Gabriele

AU - Merchant, Mark A.

AU - Sliwkowski, Mark X.

AU - deSauvage, Frederic J.

AU - Seshagiri, Somasekar

PY - 2013/5/13

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N2 - The human epidermal growth factor receptor (HER) family of tyrosine kinases is deregulated in multiple cancers either through amplification, overexpression, or mutation. ERBB3/HER3, the only member with an impaired kinase domain, although amplified or overexpressed in some cancers, has not been reported to carry oncogenic mutations. Here, we report the identification of ERBB3 somatic mutations in ~11% of colon and gastric cancers. We found that the ERBB3 mutants transformed colonic and breast epithelial cells in a ligand-independent manner. However, the mutant ERBB3 oncogenic activity was dependent on kinase-active ERBB2. Furthermore, we found that anti-ERBB antibodies and small molecule inhibitors effectively blocked mutant ERBB3-mediated oncogenic signaling and disease progression invivo.

AB - The human epidermal growth factor receptor (HER) family of tyrosine kinases is deregulated in multiple cancers either through amplification, overexpression, or mutation. ERBB3/HER3, the only member with an impaired kinase domain, although amplified or overexpressed in some cancers, has not been reported to carry oncogenic mutations. Here, we report the identification of ERBB3 somatic mutations in ~11% of colon and gastric cancers. We found that the ERBB3 mutants transformed colonic and breast epithelial cells in a ligand-independent manner. However, the mutant ERBB3 oncogenic activity was dependent on kinase-active ERBB2. Furthermore, we found that anti-ERBB antibodies and small molecule inhibitors effectively blocked mutant ERBB3-mediated oncogenic signaling and disease progression invivo.

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U2 - 10.1016/j.ccr.2013.04.012

DO - 10.1016/j.ccr.2013.04.012

M3 - Article

C2 - 23680147

AN - SCOPUS:84877839648

VL - 23

SP - 603

EP - 617

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 5

ER -

Oncogenic ERBB3 Mutations in Human Cancers

Abstract

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Oncogenic ERBB3 Mutations in Human Cancers

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