Differential Whole-genome Doubling and Homologous Recombination Deficiencies Across Breast Cancer Subtypes from the Taiwanese Population

Overview

Journal Commun Biol

Specialty Biology

Date 2021 Sep 10

PMID 34504292

Citations 4

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Karlsson E, Perez-Tenorio G, Amin R, Bostner J, Skoog L, Fornander T . The mTOR effectors 4EBP1 and S6K2 are frequently coexpressed, and associated with a poor prognosis and endocrine resistance in breast cancer: a retrospective study including patients from the randomised Stockholm tamoxifen trials. Breast Cancer Res. 2013; 15(5):R96. PMC: 3978839. DOI: 10.1186/bcr3557. View

Gaujoux R, Seoighe C . A flexible R package for nonnegative matrix factorization. BMC Bioinformatics. 2010; 11:367. PMC: 2912887. DOI: 10.1186/1471-2105-11-367. View

Davoli T, de Lange T . The causes and consequences of polyploidy in normal development and cancer. Annu Rev Cell Dev Biol. 2011; 27:585-610. DOI: 10.1146/annurev-cellbio-092910-154234. View

Lek M, Karczewski K, Minikel E, Samocha K, Banks E, Fennell T . Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016; 536(7616):285-91. PMC: 5018207. DOI: 10.1038/nature19057. View

Lin J, Fan C, Liao C, Chen Y . Taiwan Biobank: making cross-database convergence possible in the Big Data era. Gigascience. 2017; 7(1):1-4. PMC: 5774504. DOI: 10.1093/gigascience/gix110. View

Hastak K, Alli E, Ford J . Synergistic chemosensitivity of triple-negative breast cancer cell lines to poly(ADP-Ribose) polymerase inhibition, gemcitabine, and cisplatin. Cancer Res. 2010; 70(20):7970-80. PMC: 2955854. DOI: 10.1158/0008-5472.CAN-09-4521. View

Riaz N, Blecua P, Lim R, Shen R, Higginson D, Weinhold N . Pan-cancer analysis of bi-allelic alterations in homologous recombination DNA repair genes. Nat Commun. 2017; 8(1):857. PMC: 5636842. DOI: 10.1038/s41467-017-00921-w. View

Shen R, Seshan V . FACETS: allele-specific copy number and clonal heterogeneity analysis tool for high-throughput DNA sequencing. Nucleic Acids Res. 2016; 44(16):e131. PMC: 5027494. DOI: 10.1093/nar/gkw520. View

Li H, Durbin R . Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25(14):1754-60. PMC: 2705234. DOI: 10.1093/bioinformatics/btp324. View

10.

Bergstrom E, Huang M, Mahto U, Barnes M, Stratton M, Rozen S . SigProfilerMatrixGenerator: a tool for visualizing and exploring patterns of small mutational events. BMC Genomics. 2019; 20(1):685. PMC: 6717374. DOI: 10.1186/s12864-019-6041-2. View

11.

Ellrott K, Bailey M, Saksena G, Covington K, Kandoth C, Stewart C . Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines. Cell Syst. 2018; 6(3):271-281.e7. PMC: 6075717. DOI: 10.1016/j.cels.2018.03.002. View

12.

Futreal P, Coin L, Marshall M, Down T, Hubbard T, Wooster R . A census of human cancer genes. Nat Rev Cancer. 2004; 4(3):177-83. PMC: 2665285. DOI: 10.1038/nrc1299. View

13.

von Wahlde M, Timms K, Chagpar A, Wali V, Jiang T, Bossuyt V . Intratumor Heterogeneity of Homologous Recombination Deficiency in Primary Breast Cancer. Clin Cancer Res. 2016; 23(5):1193-1199. DOI: 10.1158/1078-0432.CCR-16-0889. View

14.

Vollebergh M, Lips E, Nederlof P, Wessels L, Wesseling J, Vd Vijver M . Genomic patterns resembling BRCA1- and BRCA2-mutated breast cancers predict benefit of intensified carboplatin-based chemotherapy. Breast Cancer Res. 2014; 16(3):R47. PMC: 4076636. DOI: 10.1186/bcr3655. View

15.

Lord C, Ashworth A . PARP inhibitors: Synthetic lethality in the clinic. Science. 2017; 355(6330):1152-1158. PMC: 6175050. DOI: 10.1126/science.aam7344. View

16.

Mermel C, Schumacher S, Hill B, Meyerson M, Beroukhim R, Getz G . GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers. Genome Biol. 2011; 12(4):R41. PMC: 3218867. DOI: 10.1186/gb-2011-12-4-r41. View

17.

Bailey M, Tokheim C, Porta-Pardo E, Sengupta S, Bertrand D, Weerasinghe A . Comprehensive Characterization of Cancer Driver Genes and Mutations. Cell. 2018; 173(2):371-385.e18. PMC: 6029450. DOI: 10.1016/j.cell.2018.02.060. View

18.

Carter S, Cibulskis K, Helman E, McKenna A, Shen H, Zack T . Absolute quantification of somatic DNA alterations in human cancer. Nat Biotechnol. 2012; 30(5):413-21. PMC: 4383288. DOI: 10.1038/nbt.2203. View

19.

Sondka Z, Bamford S, Cole C, Ward S, Dunham I, Forbes S . The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers. Nat Rev Cancer. 2018; 18(11):696-705. PMC: 6450507. DOI: 10.1038/s41568-018-0060-1. View

20.

Jamal-Hanjani M, Wilson G, McGranahan N, Birkbak N, Watkins T, Veeriah S . Tracking the Evolution of Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 376(22):2109-2121. DOI: 10.1056/NEJMoa1616288. View