Differential whole-genome doubling and homologous recombination deficiencies across breast cancer subtypes from the Taiwanese population

Chia Hsin Wu; Chia Shan Hsieh; Yo Cheng Chang; Chi Cheng Huang; Hsien Tang Yeh; Ming Feng Hou; Yuan Chiang Chung; Shih Hsin Tu; King Jen Chang; Amrita Chattopadhyay; Liang Chuan Lai; Tzu Pin Lu; Yung Hua Li; Mong Hsun Tsai; Eric Y. Chuang

doi:10.1038/s42003-021-02597-x

Differential whole-genome doubling and homologous recombination deficiencies across breast cancer subtypes from the Taiwanese population

Chia Hsin Wu, Chia Shan Hsieh, Yo Cheng Chang, Chi Cheng Huang, Hsien Tang Yeh, Ming Feng Hou, Yuan Chiang Chung, Shih Hsin Tu, King Jen Chang, Amrita Chattopadhyay, Liang Chuan Lai, Tzu Pin Lu, Yung Hua Li, Mong Hsun Tsai, Eric Y. Chuang

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5 Citations (Scopus)

Abstract

Whole-genome doubling (WGD) is an early macro-evolutionary event in tumorigenesis, involving the doubling of an entire chromosome complement. However, its impact on breast cancer subtypes remains unclear. Here, we performed a comprehensive and quantitative analysis of WGD and its influence on breast cancer subtypes in patients from Taiwan and consequently highlight the genomic association between WGD and homologous recombination deficiency (HRD). A higher manifestation of WGD was reported in triple-negative breast cancer, conferring high chromosomal instability (CIN), while HER2 + tumors exhibited early WGD events, with widely varied CIN levels, compared to luminal-type tumors. An association of higher activity of de novo indel signature 2 with WGD and HRD in Taiwanese breast cancer patients was reported. A control test between WGD and pseudo non-WGD samples was further employed to support this finding. The study provides a better comprehension of tumorigenesis in breast cancer subtypes, thus assisting in personalized treatment.

Original language	English
Article number	1052
Journal	Communications Biology
Volume	4
Issue number	1
DOIs	https://doi.org/10.1038/s42003-021-02597-x
Publication status	Published - Dec 2021

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry,Genetics and Molecular Biology
General Agricultural and Biological Sciences

UN SDGs

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

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10.1038/s42003-021-02597-x

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Wu, C. H., Hsieh, C. S., Chang, Y. C., Huang, C. C., Yeh, H. T., Hou, M. F., Chung, Y. C., Tu, S. H., Chang, K. J., Chattopadhyay, A., Lai, L. C., Lu, T. P., Li, Y. H., Tsai, M. H., & Chuang, E. Y. (2021). Differential whole-genome doubling and homologous recombination deficiencies across breast cancer subtypes from the Taiwanese population. Communications Biology, 4(1), Article 1052. https://doi.org/10.1038/s42003-021-02597-x

Wu, CH, Hsieh, CS, Chang, YC, Huang, CC, Yeh, HT, Hou, MF, Chung, YC, Tu, SH, Chang, KJ, Chattopadhyay, A, Lai, LC, Lu, TP, Li, YH, Tsai, MH & Chuang, EY 2021, 'Differential whole-genome doubling and homologous recombination deficiencies across breast cancer subtypes from the Taiwanese population', Communications Biology, vol. 4, no. 1, 1052. https://doi.org/10.1038/s42003-021-02597-x

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abstract = "Whole-genome doubling (WGD) is an early macro-evolutionary event in tumorigenesis, involving the doubling of an entire chromosome complement. However, its impact on breast cancer subtypes remains unclear. Here, we performed a comprehensive and quantitative analysis of WGD and its influence on breast cancer subtypes in patients from Taiwan and consequently highlight the genomic association between WGD and homologous recombination deficiency (HRD). A higher manifestation of WGD was reported in triple-negative breast cancer, conferring high chromosomal instability (CIN), while HER2 + tumors exhibited early WGD events, with widely varied CIN levels, compared to luminal-type tumors. An association of higher activity of de novo indel signature 2 with WGD and HRD in Taiwanese breast cancer patients was reported. A control test between WGD and pseudo non-WGD samples was further employed to support this finding. The study provides a better comprehension of tumorigenesis in breast cancer subtypes, thus assisting in personalized treatment.",

author = "Wu, {Chia Hsin} and Hsieh, {Chia Shan} and Chang, {Yo Cheng} and Huang, {Chi Cheng} and Yeh, {Hsien Tang} and Hou, {Ming Feng} and Chung, {Yuan Chiang} and Tu, {Shih Hsin} and Chang, {King Jen} and Amrita Chattopadhyay and Lai, {Liang Chuan} and Lu, {Tzu Pin} and Li, {Yung Hua} and Tsai, {Mong Hsun} and Chuang, {Eric Y.}",

note = "Funding Information: We would like to thank TCGA, COSMIC, Exome Aggregation Consortium, Taiwan Biobank, and The Human Protein Atlas for making their data publicly available. Finally, we thank all the participating individuals for their contribution to this study. This work was supported by the Center of Biotechnology, National Taiwan University, Taiwan [grant number GTZ300]. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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AU - Wu, Chia Hsin

AU - Hsieh, Chia Shan

AU - Chang, Yo Cheng

AU - Huang, Chi Cheng

AU - Yeh, Hsien Tang

AU - Hou, Ming Feng

AU - Chung, Yuan Chiang

AU - Tu, Shih Hsin

AU - Chang, King Jen

AU - Chattopadhyay, Amrita

AU - Lai, Liang Chuan

AU - Lu, Tzu Pin

AU - Li, Yung Hua

AU - Tsai, Mong Hsun

AU - Chuang, Eric Y.

N1 - Funding Information: We would like to thank TCGA, COSMIC, Exome Aggregation Consortium, Taiwan Biobank, and The Human Protein Atlas for making their data publicly available. Finally, we thank all the participating individuals for their contribution to this study. This work was supported by the Center of Biotechnology, National Taiwan University, Taiwan [grant number GTZ300]. Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

Y1 - 2021/12

N2 - Whole-genome doubling (WGD) is an early macro-evolutionary event in tumorigenesis, involving the doubling of an entire chromosome complement. However, its impact on breast cancer subtypes remains unclear. Here, we performed a comprehensive and quantitative analysis of WGD and its influence on breast cancer subtypes in patients from Taiwan and consequently highlight the genomic association between WGD and homologous recombination deficiency (HRD). A higher manifestation of WGD was reported in triple-negative breast cancer, conferring high chromosomal instability (CIN), while HER2 + tumors exhibited early WGD events, with widely varied CIN levels, compared to luminal-type tumors. An association of higher activity of de novo indel signature 2 with WGD and HRD in Taiwanese breast cancer patients was reported. A control test between WGD and pseudo non-WGD samples was further employed to support this finding. The study provides a better comprehension of tumorigenesis in breast cancer subtypes, thus assisting in personalized treatment.

AB - Whole-genome doubling (WGD) is an early macro-evolutionary event in tumorigenesis, involving the doubling of an entire chromosome complement. However, its impact on breast cancer subtypes remains unclear. Here, we performed a comprehensive and quantitative analysis of WGD and its influence on breast cancer subtypes in patients from Taiwan and consequently highlight the genomic association between WGD and homologous recombination deficiency (HRD). A higher manifestation of WGD was reported in triple-negative breast cancer, conferring high chromosomal instability (CIN), while HER2 + tumors exhibited early WGD events, with widely varied CIN levels, compared to luminal-type tumors. An association of higher activity of de novo indel signature 2 with WGD and HRD in Taiwanese breast cancer patients was reported. A control test between WGD and pseudo non-WGD samples was further employed to support this finding. The study provides a better comprehension of tumorigenesis in breast cancer subtypes, thus assisting in personalized treatment.

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Differential whole-genome doubling and homologous recombination deficiencies across breast cancer subtypes from the Taiwanese population

Abstract

ASJC Scopus subject areas

UN SDGs

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