Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
Genome and Systems Biology Degree Program, National Taiwan University, Taipei, Taiwan.
Commun Biol. 2021 Sep 9;4(1):1052. doi: 10.1038/s42003-021-02597-x.
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.
全基因组加倍 (WGD) 是肿瘤发生过程中的一个早期宏观进化事件，涉及整个染色体组的加倍。然而，其对乳腺癌亚型的影响尚不清楚。在这里，我们对来自台湾的患者中的 WGD 及其对乳腺癌亚型的影响进行了全面和定量的分析，从而突出了 WGD 与同源重组缺陷 (HRD) 之间的基因组关联。据报道，三阴性乳腺癌中 WGD 的表现更高，表现为高染色体不稳定性 (CIN)，而与 luminal 型肿瘤相比，HER2 阳性肿瘤表现出较早的 WGD 事件，CIN 水平差异较大。据报道，在台湾乳腺癌患者中，新的插入缺失特征 2 的更高活性与 WGD 和 HRD 相关。进一步进行了 WGD 与伪非 WGD 样本之间的对照测试，以支持这一发现。该研究提供了对乳腺癌亚型中肿瘤发生的更好理解，从而有助于个性化治疗。
