EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer

Luke Hughes-Davies; David Huntsman; Margarida Ruas; Francois Fuks; Jacqueline Bye; Suet Feung Chin; Jonathon Milner; Lindsay A. Brown; Forrest Hsu; Blake Gilks; Torsten Nielsen; Michael Schulzer; Stephen Chia; Joseph Ragaz; Anthony Cahn; Lori Linger; Hilal Ozdag; Elena Cattaneo; E. S. Jordanova; Edward Schuuring; David S. Yu; Ashok Venkitaraman; Bruce Ponder; Aidan Doherty; Samuel Aparicio; David Bentley; Charles Theillet; Chris P. Ponting; Carlos Caldas; Tony Kouzarides

doi:10.1016/S0092-8674(03)00930-9

EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer

Luke Hughes-Davies^*
, David Huntsman
, Margarida Ruas
, Francois Fuks
, Jacqueline Bye
, Suet Feung Chin
, Jonathon Milner
, Lindsay A. Brown
, Forrest Hsu
, Blake Gilks
, Torsten Nielsen
, Michael Schulzer
, Stephen Chia
, Joseph Ragaz
, Anthony Cahn
, Lori Linger
, Hilal Ozdag
, Elena Cattaneo
, E. S. Jordanova
, Edward Schuuring

David S. Yu, Ashok Venkitaraman, Bruce Ponder, Aidan Doherty, Samuel Aparicio, David Bentley, Charles Theillet, Chris P. Ponting, Carlos Caldas, Tony Kouzarides

^*Corresponding author for this work

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

384 Scopus citations

Abstract

The BRCA2 gene is mutated in familial breast and ovarian cancer, and its product is implicated in DNA repair and transcriptional regulation. Here we identify a protein, EMSY, which binds BRCA2 within a region (exon 3) deleted in cancer. EMSY is capable of silencing the activation potential of BRCA2 exon 3, associates with chromatin regulators HP1β and BS69, and localizes to sites of repair following DNA damage. EMSY maps to chromosome 11q13.5, a region known to be involved in breast and ovarian cancer. We show that the EMSY gene is amplified almost exclusively in sporadic breast cancer (13%) and higher-grade ovarian cancer (17%). In addition, EMSY amplification is associated with worse survival, particularly in node-negative breast cancer, suggesting that it may be of prognostic value. The remarkable clinical overlap between sporadic EMSY amplification and familial BRCA2 deletion implicates a BRCA2 pathway in sporadic breast and ovarian cancer.

Original language	English
Pages (from-to)	523-535
Number of pages	13
Journal	Cell
Volume	115
Issue number	5
DOIs	https://doi.org/10.1016/S0092-8674(03)00930-9
State	Published - 26 Nov 2003
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1016/S0092-8674(03)00930-9

Cite this

Hughes-Davies, L., Huntsman, D., Ruas, M., Fuks, F., Bye, J., Chin, S. F., Milner, J., Brown, L. A., Hsu, F., Gilks, B., Nielsen, T., Schulzer, M., Chia, S., Ragaz, J., Cahn, A., Linger, L., Ozdag, H., Cattaneo, E., Jordanova, E. S., ... Kouzarides, T. (2003). EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer. Cell, 115(5), 523-535. https://doi.org/10.1016/S0092-8674(03)00930-9

@article{447653c97081419e8db996ccb3456056,

title = "EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer",

abstract = "The BRCA2 gene is mutated in familial breast and ovarian cancer, and its product is implicated in DNA repair and transcriptional regulation. Here we identify a protein, EMSY, which binds BRCA2 within a region (exon 3) deleted in cancer. EMSY is capable of silencing the activation potential of BRCA2 exon 3, associates with chromatin regulators HP1β and BS69, and localizes to sites of repair following DNA damage. EMSY maps to chromosome 11q13.5, a region known to be involved in breast and ovarian cancer. We show that the EMSY gene is amplified almost exclusively in sporadic breast cancer (13\%) and higher-grade ovarian cancer (17\%). In addition, EMSY amplification is associated with worse survival, particularly in node-negative breast cancer, suggesting that it may be of prognostic value. The remarkable clinical overlap between sporadic EMSY amplification and familial BRCA2 deletion implicates a BRCA2 pathway in sporadic breast and ovarian cancer.",

author = "Luke Hughes-Davies and David Huntsman and Margarida Ruas and Francois Fuks and Jacqueline Bye and Chin, \{Suet Feung\} and Jonathon Milner and Brown, \{Lindsay A.\} and Forrest Hsu and Blake Gilks and Torsten Nielsen and Michael Schulzer and Stephen Chia and Joseph Ragaz and Anthony Cahn and Lori Linger and Hilal Ozdag and Elena Cattaneo and Jordanova, \{E. S.\} and Edward Schuuring and Yu, \{David S.\} and Ashok Venkitaraman and Bruce Ponder and Aidan Doherty and Samuel Aparicio and David Bentley and Charles Theillet and Ponting, \{Chris P.\} and Carlos Caldas and Tony Kouzarides",

year = "2003",

month = nov,

day = "26",

doi = "10.1016/S0092-8674(03)00930-9",

language = "אנגלית",

volume = "115",

pages = "523--535",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "5",

}

Hughes-Davies, L, Huntsman, D, Ruas, M, Fuks, F, Bye, J, Chin, SF, Milner, J, Brown, LA, Hsu, F, Gilks, B, Nielsen, T, Schulzer, M, Chia, S, Ragaz, J, Cahn, A, Linger, L, Ozdag, H, Cattaneo, E, Jordanova, ES, Schuuring, E, Yu, DS, Venkitaraman, A, Ponder, B, Doherty, A, Aparicio, S, Bentley, D, Theillet, C, Ponting, CP, Caldas, C & Kouzarides, T 2003, 'EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer', Cell, vol. 115, no. 5, pp. 523-535. https://doi.org/10.1016/S0092-8674(03)00930-9

TY - JOUR

T1 - EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer

AU - Hughes-Davies, Luke

AU - Huntsman, David

AU - Ruas, Margarida

AU - Fuks, Francois

AU - Bye, Jacqueline

AU - Chin, Suet Feung

AU - Milner, Jonathon

AU - Brown, Lindsay A.

AU - Hsu, Forrest

AU - Gilks, Blake

AU - Nielsen, Torsten

AU - Schulzer, Michael

AU - Chia, Stephen

AU - Ragaz, Joseph

AU - Cahn, Anthony

AU - Linger, Lori

AU - Ozdag, Hilal

AU - Cattaneo, Elena

AU - Jordanova, E. S.

AU - Schuuring, Edward

AU - Yu, David S.

AU - Venkitaraman, Ashok

AU - Ponder, Bruce

AU - Doherty, Aidan

AU - Aparicio, Samuel

AU - Bentley, David

AU - Theillet, Charles

AU - Ponting, Chris P.

AU - Caldas, Carlos

AU - Kouzarides, Tony

PY - 2003/11/26

Y1 - 2003/11/26

N2 - The BRCA2 gene is mutated in familial breast and ovarian cancer, and its product is implicated in DNA repair and transcriptional regulation. Here we identify a protein, EMSY, which binds BRCA2 within a region (exon 3) deleted in cancer. EMSY is capable of silencing the activation potential of BRCA2 exon 3, associates with chromatin regulators HP1β and BS69, and localizes to sites of repair following DNA damage. EMSY maps to chromosome 11q13.5, a region known to be involved in breast and ovarian cancer. We show that the EMSY gene is amplified almost exclusively in sporadic breast cancer (13%) and higher-grade ovarian cancer (17%). In addition, EMSY amplification is associated with worse survival, particularly in node-negative breast cancer, suggesting that it may be of prognostic value. The remarkable clinical overlap between sporadic EMSY amplification and familial BRCA2 deletion implicates a BRCA2 pathway in sporadic breast and ovarian cancer.

AB - The BRCA2 gene is mutated in familial breast and ovarian cancer, and its product is implicated in DNA repair and transcriptional regulation. Here we identify a protein, EMSY, which binds BRCA2 within a region (exon 3) deleted in cancer. EMSY is capable of silencing the activation potential of BRCA2 exon 3, associates with chromatin regulators HP1β and BS69, and localizes to sites of repair following DNA damage. EMSY maps to chromosome 11q13.5, a region known to be involved in breast and ovarian cancer. We show that the EMSY gene is amplified almost exclusively in sporadic breast cancer (13%) and higher-grade ovarian cancer (17%). In addition, EMSY amplification is associated with worse survival, particularly in node-negative breast cancer, suggesting that it may be of prognostic value. The remarkable clinical overlap between sporadic EMSY amplification and familial BRCA2 deletion implicates a BRCA2 pathway in sporadic breast and ovarian cancer.

UR - https://www.scopus.com/pages/publications/10744233204

U2 - 10.1016/S0092-8674(03)00930-9

DO - 10.1016/S0092-8674(03)00930-9

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 14651845

AN - SCOPUS:10744233204

SN - 0092-8674

VL - 115

SP - 523

EP - 535

JO - Cell

JF - Cell

IS - 5

ER -

EMSY Links the BRCA2 Pathway to Sporadic Breast and Ovarian Cancer

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this