-transparent.png){kind=logo}
Bi-allelic alterations in DNA repair genes underpin homologous recombination DNA repair defects in breast cancer. 2017
Robert W Mutter, and
Nadeem Riaz, and
Charlotte Ky Ng, and
Rob Delsite, and
Salvatore Piscuoglio, and
Marcia Edelweiss, and
Luciano G Martelotto, and
Rita A Sakr, and
Tari A King, and
Dilip D Giri, and
Maria Drobnjak, and
Edi Brogi, and
Ranjit Bindra, and
Giana Bernheim, and
Raymond S Lim, and
Pedro Blecua, and
Alexis Desrichard, and
Dan Higginson, and
Russell Towers, and
Ruomu Jiang, and
William Lee, and
Britta Weigelt, and
Jorge S Reis-Filho, and
Simon N Powell
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Homologous recombination (HR) DNA repair-deficient (HRD) breast cancers have been shown to be sensitive to DNA repair targeted therapies. Burgeoning evidence suggests that sporadic breast cancers, lacking germline BRCA1/BRCA2 mutations, may also be HRD. We developed a functional ex vivo RAD51-based test to identify HRD primary breast cancers. An integrated approach examining methylation, gene expression, and whole-exome sequencing was employed to ascertain the aetiology of HRD. Functional HRD breast cancers displayed genomic features of lack of competent HR, including large-scale state transitions and specific mutational signatures. Somatic and/or germline genetic alterations resulting in bi-allelic loss-of-function of HR genes underpinned functional HRD in 89% of cases, and were observed in only one of the 15 HR-proficient samples tested. These findings indicate the importance of a comprehensive genetic assessment of bi-allelic alterations in the HR pathway to deliver a precision medicine-based approach to select patients for therapies targeting tumour-specific DNA repair defects. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Related Publications
Robert W Mutter, and
Nadeem Riaz, and
Charlotte Ky Ng, and
Rob Delsite, and
Salvatore Piscuoglio, and
Marcia Edelweiss, and
Luciano G Martelotto, and
Rita A Sakr, and
Tari A King, and
Dilip D Giri, and
Maria Drobnjak, and
Edi Brogi, and
Ranjit Bindra, and
Giana Bernheim, and
Raymond S Lim, and
Pedro Blecua, and
Alexis Desrichard, and
Dan Higginson, and
Russell Towers, and
Ruomu Jiang, and
William Lee, and
Britta Weigelt, and
Jorge S Reis-Filho, and
Simon N Powell
October 2017,
Nature communications,
Robert W Mutter, and
Nadeem Riaz, and
Charlotte Ky Ng, and
Rob Delsite, and
Salvatore Piscuoglio, and
Marcia Edelweiss, and
Luciano G Martelotto, and
Rita A Sakr, and
Tari A King, and
Dilip D Giri, and
Maria Drobnjak, and
Edi Brogi, and
Ranjit Bindra, and
Giana Bernheim, and
Raymond S Lim, and
Pedro Blecua, and
Alexis Desrichard, and
Dan Higginson, and
Russell Towers, and
Ruomu Jiang, and
William Lee, and
Britta Weigelt, and
Jorge S Reis-Filho, and
Simon N Powell
April 2020,
International journal of molecular sciences,
Robert W Mutter, and
Nadeem Riaz, and
Charlotte Ky Ng, and
Rob Delsite, and
Salvatore Piscuoglio, and
Marcia Edelweiss, and
Luciano G Martelotto, and
Rita A Sakr, and
Tari A King, and
Dilip D Giri, and
Maria Drobnjak, and
Edi Brogi, and
Ranjit Bindra, and
Giana Bernheim, and
Raymond S Lim, and
Pedro Blecua, and
Alexis Desrichard, and
Dan Higginson, and
Russell Towers, and
Ruomu Jiang, and
William Lee, and
Britta Weigelt, and
Jorge S Reis-Filho, and
Simon N Powell
January 2019,
NPJ breast cancer,
Robert W Mutter, and
Nadeem Riaz, and
Charlotte Ky Ng, and
Rob Delsite, and
Salvatore Piscuoglio, and
Marcia Edelweiss, and
Luciano G Martelotto, and
Rita A Sakr, and
Tari A King, and
Dilip D Giri, and
Maria Drobnjak, and
Edi Brogi, and
Ranjit Bindra, and
Giana Bernheim, and
Raymond S Lim, and
Pedro Blecua, and
Alexis Desrichard, and
Dan Higginson, and
Russell Towers, and
Ruomu Jiang, and
William Lee, and
Britta Weigelt, and
Jorge S Reis-Filho, and
Simon N Powell
May 2022,
Nature communications,
Robert W Mutter, and
Nadeem Riaz, and
Charlotte Ky Ng, and
Rob Delsite, and
Salvatore Piscuoglio, and
Marcia Edelweiss, and
Luciano G Martelotto, and
Rita A Sakr, and
Tari A King, and
Dilip D Giri, and
Maria Drobnjak, and
Edi Brogi, and
Ranjit Bindra, and
Giana Bernheim, and
Raymond S Lim, and
Pedro Blecua, and
Alexis Desrichard, and
Dan Higginson, and
Russell Towers, and
Ruomu Jiang, and
William Lee, and
Britta Weigelt, and
Jorge S Reis-Filho, and
Simon N Powell
August 2010,
Trends in pharmacological sciences,
Robert W Mutter, and
Nadeem Riaz, and
Charlotte Ky Ng, and
Rob Delsite, and
Salvatore Piscuoglio, and
Marcia Edelweiss, and
Luciano G Martelotto, and
Rita A Sakr, and
Tari A King, and
Dilip D Giri, and
Maria Drobnjak, and
Edi Brogi, and
Ranjit Bindra, and
Giana Bernheim, and
Raymond S Lim, and
Pedro Blecua, and
Alexis Desrichard, and
Dan Higginson, and
Russell Towers, and
Ruomu Jiang, and
William Lee, and
Britta Weigelt, and
Jorge S Reis-Filho, and
Simon N Powell
January 2019,
NPJ breast cancer,
Robert W Mutter, and
Nadeem Riaz, and
Charlotte Ky Ng, and
Rob Delsite, and
Salvatore Piscuoglio, and
Marcia Edelweiss, and
Luciano G Martelotto, and
Rita A Sakr, and
Tari A King, and
Dilip D Giri, and
Maria Drobnjak, and
Edi Brogi, and
Ranjit Bindra, and
Giana Bernheim, and
Raymond S Lim, and
Pedro Blecua, and
Alexis Desrichard, and
Dan Higginson, and
Russell Towers, and
Ruomu Jiang, and
William Lee, and
Britta Weigelt, and
Jorge S Reis-Filho, and
Simon N Powell
June 2022,
Annals of surgical oncology,
Robert W Mutter, and
Nadeem Riaz, and
Charlotte Ky Ng, and
Rob Delsite, and
Salvatore Piscuoglio, and
Marcia Edelweiss, and
Luciano G Martelotto, and
Rita A Sakr, and
Tari A King, and
Dilip D Giri, and
Maria Drobnjak, and
Edi Brogi, and
Ranjit Bindra, and
Giana Bernheim, and
Raymond S Lim, and
Pedro Blecua, and
Alexis Desrichard, and
Dan Higginson, and
Russell Towers, and
Ruomu Jiang, and
William Lee, and
Britta Weigelt, and
Jorge S Reis-Filho, and
Simon N Powell
October 2019,
Pathology oncology research : POR,
Robert W Mutter, and
Nadeem Riaz, and
Charlotte Ky Ng, and
Rob Delsite, and
Salvatore Piscuoglio, and
Marcia Edelweiss, and
Luciano G Martelotto, and
Rita A Sakr, and
Tari A King, and
Dilip D Giri, and
Maria Drobnjak, and
Edi Brogi, and
Ranjit Bindra, and
Giana Bernheim, and
Raymond S Lim, and
Pedro Blecua, and
Alexis Desrichard, and
Dan Higginson, and
Russell Towers, and
Ruomu Jiang, and
William Lee, and
Britta Weigelt, and
Jorge S Reis-Filho, and
Simon N Powell
October 2017,
Nature genetics,
Robert W Mutter, and
Nadeem Riaz, and
Charlotte Ky Ng, and
Rob Delsite, and
Salvatore Piscuoglio, and
Marcia Edelweiss, and
Luciano G Martelotto, and
Rita A Sakr, and
Tari A King, and
Dilip D Giri, and
Maria Drobnjak, and
Edi Brogi, and
Ranjit Bindra, and
Giana Bernheim, and
Raymond S Lim, and
Pedro Blecua, and
Alexis Desrichard, and
Dan Higginson, and
Russell Towers, and
Ruomu Jiang, and
William Lee, and
Britta Weigelt, and
Jorge S Reis-Filho, and
Simon N Powell
January 2016,
Breast cancer research and treatment,
