Cancer Research Malaysia, No. 1, Jalan SS12/1A, 47500, Subang Jaya, Malaysia.
Subang Jaya Medical Centre, No. 1, Jalan SS12/1A, 47500, Subang Jaya, Malaysia.
Breast Cancer Res. 2023 Apr 26;25(1):48. doi: 10.1186/s13058-023-01635-2.
Recent genomics studies of breast cancer in Asian cohorts have found a higher prevalence of TP53 mutations in Asian breast cancer patients relative to Caucasian patients. However, the effect of TP53 mutations on Asian breast tumours has not been comprehensively studied.
Here, we report an analysis of 492 breast cancer samples from the Malaysian Breast Cancer cohort where we examined the impact of TP53 somatic mutations in relation to PAM50 subtypes by comparing whole exome and transcriptome data from tumours with mutant and wild-type TP53.
We found that the magnitude of impact of TP53 somatic mutations appears to vary between different subtypes. TP53 somatic mutations were associated with higher HR deficiency scores as well as greater upregulation of gene expression pathways in luminal A and luminal B tumours compared to the basal-like and Her2-enriched subtypes. The only pathways that were consistently dysregulated when comparing tumours with mutant and wild-type TP53 across different subtypes were the mTORC1 signalling and glycolysis pathways.
These results suggest that therapies that target TP53 or other downstream pathways may be more effective against luminal A and B tumours in the Asian population.
最近亚洲队列的乳腺癌基因组学研究发现，亚洲乳腺癌患者中 TP53 突变的发生率高于高加索患者。然而，TP53 突变对亚洲乳腺癌的影响尚未得到全面研究。
本研究报告了对马来西亚乳腺癌队列中的 492 个乳腺癌样本进行的分析，我们通过比较肿瘤中突变型和野生型 TP53 的全外显子组和转录组数据，研究了 TP53 体细胞突变与 PAM50 亚型之间的关系。
我们发现，TP53 体细胞突变的影响程度似乎在不同亚型之间存在差异。与基底样和 Her2 富集亚型相比，TP53 体细胞突变与 luminal A 和 luminal B 肿瘤中更高的 HR 缺陷评分以及更大的基因表达途径上调相关。在比较不同亚型中突变型和野生型 TP53 的肿瘤时，唯一始终失调的途径是 mTORC1 信号和糖酵解途径。
这些结果表明，针对 TP53 或其他下游途径的治疗方法可能对亚洲人群中的 luminal A 和 B 肿瘤更有效。
