TP53 somatic mutations in Asian breast cancer are associated with subtype-specific effects
Abstract Background 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. Methods H...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-023-01635-2 |
| _version_ | 1797836181427191808 |
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| author | Mohana Eswari Ragu Joanna Mei Ch’wan Lim Pei-Sze Ng Cheng-Har Yip Pathmanathan Rajadurai Soo-Hwang Teo Jia-Wern Pan |
| author_facet | Mohana Eswari Ragu Joanna Mei Ch’wan Lim Pei-Sze Ng Cheng-Har Yip Pathmanathan Rajadurai Soo-Hwang Teo Jia-Wern Pan |
| author_sort | Mohana Eswari Ragu |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusion 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. |
| first_indexed | 2024-04-09T15:05:39Z |
| format | Article |
| id | doaj.art-e2a9a5d4c3e54315b9693ca107bf1b7e |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-04-09T15:05:39Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-e2a9a5d4c3e54315b9693ca107bf1b7e2023-04-30T11:32:15ZengBMCBreast Cancer Research1465-542X2023-04-0125111210.1186/s13058-023-01635-2TP53 somatic mutations in Asian breast cancer are associated with subtype-specific effectsMohana Eswari Ragu0Joanna Mei Ch’wan Lim1Pei-Sze Ng2Cheng-Har Yip3Pathmanathan Rajadurai4Soo-Hwang Teo5Jia-Wern Pan6Cancer Research MalaysiaCancer Research MalaysiaCancer Research MalaysiaSubang Jaya Medical CentreSubang Jaya Medical CentreCancer Research MalaysiaCancer Research MalaysiaAbstract Background 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. Methods 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. Results 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. Conclusion 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.https://doi.org/10.1186/s13058-023-01635-2TP53Breast cancerAsian population |
| spellingShingle | Mohana Eswari Ragu Joanna Mei Ch’wan Lim Pei-Sze Ng Cheng-Har Yip Pathmanathan Rajadurai Soo-Hwang Teo Jia-Wern Pan TP53 somatic mutations in Asian breast cancer are associated with subtype-specific effects Breast Cancer Research TP53 Breast cancer Asian population |
| title | TP53 somatic mutations in Asian breast cancer are associated with subtype-specific effects |
| title_full | TP53 somatic mutations in Asian breast cancer are associated with subtype-specific effects |
| title_fullStr | TP53 somatic mutations in Asian breast cancer are associated with subtype-specific effects |
| title_full_unstemmed | TP53 somatic mutations in Asian breast cancer are associated with subtype-specific effects |
| title_short | TP53 somatic mutations in Asian breast cancer are associated with subtype-specific effects |
| title_sort | tp53 somatic mutations in asian breast cancer are associated with subtype specific effects |
| topic | TP53 Breast cancer Asian population |
| url | https://doi.org/10.1186/s13058-023-01635-2 |
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