Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients
Early onset breast cancer (EOBC), diagnosed at age ~40 or younger, is associated with a poorer prognosis and higher mortality rate compared to breast cancer diagnosed at age 50 or older. EOBC poses a serious threat to public health and requires in-depth investigation. We studied a cohort comprising...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/8/2089 |
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| author | Mohit K. Midha Yu-Feng Huang Hsiao-Hsiang Yang Tan-Chi Fan Nai-Chuan Chang Tzu-Han Chen Yu-Tai Wang Wen-Hung Kuo King-Jen Chang Chen-Yang Shen Alice L. Yu Kuo-Ping Chiu Chien-Jen Chen |
| author_facet | Mohit K. Midha Yu-Feng Huang Hsiao-Hsiang Yang Tan-Chi Fan Nai-Chuan Chang Tzu-Han Chen Yu-Tai Wang Wen-Hung Kuo King-Jen Chang Chen-Yang Shen Alice L. Yu Kuo-Ping Chiu Chien-Jen Chen |
| author_sort | Mohit K. Midha |
| collection | DOAJ |
| description | Early onset breast cancer (EOBC), diagnosed at age ~40 or younger, is associated with a poorer prognosis and higher mortality rate compared to breast cancer diagnosed at age 50 or older. EOBC poses a serious threat to public health and requires in-depth investigation. We studied a cohort comprising 90 Taiwanese female patients, aiming to unravel the underlying mechanisms of EOBC etiopathogenesis. Sequence data generated by whole-exome sequencing (WES) and whole-genome sequencing (WGS) from white blood cell (WBC)–tumor pairs were analyzed to identify somatic missense mutations, copy number variations (CNVs) and germline missense mutations. Similar to regular breast cancer, the key somatic mutation-susceptibility genes of EOBC include <i>TP53</i> (40% prevalence), <i>PIK3CA</i> (37%), <i>GATA3</i> (17%) and <i>KMT2C</i> (17%), which are frequently reported in breast cancer; however, the structural protein-coding genes <i>MUC17</i> (19%), <i>FLG</i> (16%) and <i>NEBL</i> (11%) show a significantly higher prevalence in EOBC. Furthermore, the top 2 genes harboring EOBC germline mutations, <i>MUC16</i> (19%) and <i>KRT18</i> (19%), encode structural proteins. Compared to conventional breast cancer, an unexpectedly higher number of EOBC susceptibility genes encode structural proteins. We suspect that mutations in structural proteins may increase physical permeability to environmental hormones and carcinogens and cause breast cancer to occur at a young age. |
| first_indexed | 2024-03-10T18:10:32Z |
| format | Article |
| id | doaj.art-ddd7f4fa038c4b96906028c7a4fc10da |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:10:32Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ddd7f4fa038c4b96906028c7a4fc10da2023-11-20T08:12:09ZengMDPI AGCancers2072-66942020-07-01128208910.3390/cancers12082089Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer PatientsMohit K. Midha0Yu-Feng Huang1Hsiao-Hsiang Yang2Tan-Chi Fan3Nai-Chuan Chang4Tzu-Han Chen5Yu-Tai Wang6Wen-Hung Kuo7King-Jen Chang8Chen-Yang Shen9Alice L. Yu10Kuo-Ping Chiu11Chien-Jen Chen12Genomics Research Center, Academia Sinica, Taipei 11529, TaiwanGenomics Research Center, Academia Sinica, Taipei 11529, TaiwanDepartment of Medical Research, Hsinchu Mackay Memorial Hospital, Hsinchu 300, TaiwanInstitute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou and Chang Gung University, No. 5, Fu-Shin St., Kuei Shang, Taoyuan 333, TaiwanInstitute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou and Chang Gung University, No. 5, Fu-Shin St., Kuei Shang, Taoyuan 333, TaiwanGenomics Research Center, Academia Sinica, Taipei 11529, TaiwanNational Center for High-Performance Computing, Hsinchu Science Park, Hsinchu 300, TaiwanDepartment of Surgery, National Taiwan University Hospital, Taipei 100, TaiwanDepartment of Surgery, National Taiwan University Hospital, Taipei 100, TaiwanInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, TaiwanInstitute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou and Chang Gung University, No. 5, Fu-Shin St., Kuei Shang, Taoyuan 333, TaiwanGenomics Research Center, Academia Sinica, Taipei 11529, TaiwanGenomics Research Center, Academia Sinica, Taipei 11529, TaiwanEarly onset breast cancer (EOBC), diagnosed at age ~40 or younger, is associated with a poorer prognosis and higher mortality rate compared to breast cancer diagnosed at age 50 or older. EOBC poses a serious threat to public health and requires in-depth investigation. We studied a cohort comprising 90 Taiwanese female patients, aiming to unravel the underlying mechanisms of EOBC etiopathogenesis. Sequence data generated by whole-exome sequencing (WES) and whole-genome sequencing (WGS) from white blood cell (WBC)–tumor pairs were analyzed to identify somatic missense mutations, copy number variations (CNVs) and germline missense mutations. Similar to regular breast cancer, the key somatic mutation-susceptibility genes of EOBC include <i>TP53</i> (40% prevalence), <i>PIK3CA</i> (37%), <i>GATA3</i> (17%) and <i>KMT2C</i> (17%), which are frequently reported in breast cancer; however, the structural protein-coding genes <i>MUC17</i> (19%), <i>FLG</i> (16%) and <i>NEBL</i> (11%) show a significantly higher prevalence in EOBC. Furthermore, the top 2 genes harboring EOBC germline mutations, <i>MUC16</i> (19%) and <i>KRT18</i> (19%), encode structural proteins. Compared to conventional breast cancer, an unexpectedly higher number of EOBC susceptibility genes encode structural proteins. We suspect that mutations in structural proteins may increase physical permeability to environmental hormones and carcinogens and cause breast cancer to occur at a young age.https://www.mdpi.com/2072-6694/12/8/2089early onset breast cancer (EOBC)missense mutationsnonsynonymous mutationssomatic mutationsgermline mutations |
| spellingShingle | Mohit K. Midha Yu-Feng Huang Hsiao-Hsiang Yang Tan-Chi Fan Nai-Chuan Chang Tzu-Han Chen Yu-Tai Wang Wen-Hung Kuo King-Jen Chang Chen-Yang Shen Alice L. Yu Kuo-Ping Chiu Chien-Jen Chen Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients Cancers early onset breast cancer (EOBC) missense mutations nonsynonymous mutations somatic mutations germline mutations |
| title | Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients |
| title_full | Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients |
| title_fullStr | Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients |
| title_full_unstemmed | Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients |
| title_short | Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients |
| title_sort | comprehensive cohort analysis of mutational spectrum in early onset breast cancer patients |
| topic | early onset breast cancer (EOBC) missense mutations nonsynonymous mutations somatic mutations germline mutations |
| url | https://www.mdpi.com/2072-6694/12/8/2089 |
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