TP53 somatic mutations in Asian breast cancer are associated with subtype-specific effects

TP53 somatic mutations in Asian breast cancer are associated with subtype-specific effects

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 o...

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Published in:Breast cancer research : BCR Vol. 25; no. 1; p. 48
Main Authors: Ragu, Mohana Eswari, Lim, Joanna Mei Ch'wan, Ng, Pei-Sze, Yip, Cheng-Har, Rajadurai, Pathmanathan, Teo, Soo-Hwang, Pan, Jia-Wern
Format: Journal Article
Language:English
Published: England BioMed Central 26-04-2023
BMC
Subjects:
Asian People - genetics
Asian population
Biomarkers, Tumor - genetics
Breast cancer
Breast Neoplasms - pathology
Cell cycle
DNA repair
ErbB-2 protein
Female
Gene expression
Genes, erbB-2
Genomics
Glycolysis
Humans
Medical prognosis
Mutants
Mutation
p53 Protein
Patients
Proteins
Signal transduction
TP53
Transcriptome
Transcriptomes
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Tumors
White people
Asian population
TP53
Breast cancer
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Summary: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.
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ISSN:1465-542X
1465-5411
1465-542X
DOI:10.1186/s13058-023-01635-2