Tumor mutational profile of triple negative breast cancer patients in Thailand revealed distinctive genetic alteration in chromatin remodeling gene
Background Triple negative breast cancer (TNBC) is a breast cancer subtype characterized by absence of both hormonal receptors and human epithelial growth factor receptor 2 (HER2). TNBC accounts for 15–20% of breast cancer. TNBC is associated with more aggressive disease and worse clinical outcome....
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PeerJ Inc.
2019-02-01
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| Online Access: | https://peerj.com/articles/6501.pdf |
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| author | Suvimol Niyomnaitham Napa Parinyanitikul Ekkapong Roothumnong Worapoj Jinda Norasate Samarnthai Taywin Atikankul Bhoom Suktitipat Wanna Thongnoppakhun Chanin Limwongse Manop Pithukpakorn |
| author_facet | Suvimol Niyomnaitham Napa Parinyanitikul Ekkapong Roothumnong Worapoj Jinda Norasate Samarnthai Taywin Atikankul Bhoom Suktitipat Wanna Thongnoppakhun Chanin Limwongse Manop Pithukpakorn |
| author_sort | Suvimol Niyomnaitham |
| collection | DOAJ |
| description | Background Triple negative breast cancer (TNBC) is a breast cancer subtype characterized by absence of both hormonal receptors and human epithelial growth factor receptor 2 (HER2). TNBC accounts for 15–20% of breast cancer. TNBC is associated with more aggressive disease and worse clinical outcome. Though the underlying mechanism of TNBC is currently unclear, the heterogeneity of clinical characteristics in various population may relate to the difference in tumor mutational profile. There were studies on TNBC gene mutations in various ethnic groups but the tumor genome data on Thai TNBC patients is currently unknown. This study aims to investigate mutational profile of Thai TNBC. Methods The patients were Thai individuals who were diagnosed with primary breast carcinoma between 2014 and 2017. All surgically removed primary tumor tissues were carefully examined by pathologists and archived as formalin-fixed paraffin-embedded tumor. TNBC was defined by absence of hormonal receptors and HER2 by immunohistochemistry. Genomic DNA was extracted, enriched and sequenced of all exomes on the Illumina HiSeq. Genomic data were then processed through bioinformatics platform to identify genomic alterations and tumor mutational burden. Results A total of 116 TNBC patients were recruited. Genomic analysis of TNBC samples identified 81,460 variants, of which 5,906 variants were in cancer-associated genes. The result showed that Thai TNBC has higher tumor mutation burden than previously reported data. The most frequently mutated cancer-associated gene was TP53 similar to other TNBC cohorts. Meanwhile KMT2C was found to be more commonly mutated in Thai TNBC than previous studies. Mutational profile of Thai TNBC patients also revealed difference in many frequently mutated genes when compared to other Western TNBC cohorts. Conclusion This result supported that TNBC breast cancer patients from various ethnic background showed diverse genome alteration pattern. Although TP53 is the most commonly mutated gene across all cohorts, Thai TNBC showed different gene mutation frequencies, especially in KMT2C. In particular, the cancer gene mutations are more prevalent in Thai TNBC patients. This result provides important insight on diverse underlying genetic and epigenetic mechanisms of TNBC that could translate to a new treatment strategy for patients with this disease. |
| first_indexed | 2024-03-09T08:20:30Z |
| format | Article |
| id | doaj.art-31a4b574358745fba8ee20ccc033470b |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T08:20:30Z |
| publishDate | 2019-02-01 |
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| spelling | doaj.art-31a4b574358745fba8ee20ccc033470b2023-12-02T21:50:06ZengPeerJ Inc.PeerJ2167-83592019-02-017e650110.7717/peerj.6501Tumor mutational profile of triple negative breast cancer patients in Thailand revealed distinctive genetic alteration in chromatin remodeling geneSuvimol Niyomnaitham0Napa Parinyanitikul1Ekkapong Roothumnong2Worapoj Jinda3Norasate Samarnthai4Taywin Atikankul5Bhoom Suktitipat6Wanna Thongnoppakhun7Chanin Limwongse8Manop Pithukpakorn9Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDepartment of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandDepartment of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandSiriraj Center of Research Excellence in Precision Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDepartment of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDepartment of Pathology, Queen Savang Vadhana Memorial Hospital, Thai Red Cross Society, Chonburi, ThailandSiriraj Center of Research Excellence in Precision Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandSiriraj Center of Research Excellence in Precision Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDepartment of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDepartment of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandBackground Triple negative breast cancer (TNBC) is a breast cancer subtype characterized by absence of both hormonal receptors and human epithelial growth factor receptor 2 (HER2). TNBC accounts for 15–20% of breast cancer. TNBC is associated with more aggressive disease and worse clinical outcome. Though the underlying mechanism of TNBC is currently unclear, the heterogeneity of clinical characteristics in various population may relate to the difference in tumor mutational profile. There were studies on TNBC gene mutations in various ethnic groups but the tumor genome data on Thai TNBC patients is currently unknown. This study aims to investigate mutational profile of Thai TNBC. Methods The patients were Thai individuals who were diagnosed with primary breast carcinoma between 2014 and 2017. All surgically removed primary tumor tissues were carefully examined by pathologists and archived as formalin-fixed paraffin-embedded tumor. TNBC was defined by absence of hormonal receptors and HER2 by immunohistochemistry. Genomic DNA was extracted, enriched and sequenced of all exomes on the Illumina HiSeq. Genomic data were then processed through bioinformatics platform to identify genomic alterations and tumor mutational burden. Results A total of 116 TNBC patients were recruited. Genomic analysis of TNBC samples identified 81,460 variants, of which 5,906 variants were in cancer-associated genes. The result showed that Thai TNBC has higher tumor mutation burden than previously reported data. The most frequently mutated cancer-associated gene was TP53 similar to other TNBC cohorts. Meanwhile KMT2C was found to be more commonly mutated in Thai TNBC than previous studies. Mutational profile of Thai TNBC patients also revealed difference in many frequently mutated genes when compared to other Western TNBC cohorts. Conclusion This result supported that TNBC breast cancer patients from various ethnic background showed diverse genome alteration pattern. Although TP53 is the most commonly mutated gene across all cohorts, Thai TNBC showed different gene mutation frequencies, especially in KMT2C. In particular, the cancer gene mutations are more prevalent in Thai TNBC patients. This result provides important insight on diverse underlying genetic and epigenetic mechanisms of TNBC that could translate to a new treatment strategy for patients with this disease.https://peerj.com/articles/6501.pdfBreastCancerThaiAsianGenomeHistone |
| spellingShingle | Suvimol Niyomnaitham Napa Parinyanitikul Ekkapong Roothumnong Worapoj Jinda Norasate Samarnthai Taywin Atikankul Bhoom Suktitipat Wanna Thongnoppakhun Chanin Limwongse Manop Pithukpakorn Tumor mutational profile of triple negative breast cancer patients in Thailand revealed distinctive genetic alteration in chromatin remodeling gene PeerJ Breast Cancer Thai Asian Genome Histone |
| title | Tumor mutational profile of triple negative breast cancer patients in Thailand revealed distinctive genetic alteration in chromatin remodeling gene |
| title_full | Tumor mutational profile of triple negative breast cancer patients in Thailand revealed distinctive genetic alteration in chromatin remodeling gene |
| title_fullStr | Tumor mutational profile of triple negative breast cancer patients in Thailand revealed distinctive genetic alteration in chromatin remodeling gene |
| title_full_unstemmed | Tumor mutational profile of triple negative breast cancer patients in Thailand revealed distinctive genetic alteration in chromatin remodeling gene |
| title_short | Tumor mutational profile of triple negative breast cancer patients in Thailand revealed distinctive genetic alteration in chromatin remodeling gene |
| title_sort | tumor mutational profile of triple negative breast cancer patients in thailand revealed distinctive genetic alteration in chromatin remodeling gene |
| topic | Breast Cancer Thai Asian Genome Histone |
| url | https://peerj.com/articles/6501.pdf |
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