Mutational landscape differences between young-onset and older-onset breast cancer patients
Abstract Background The incidence of breast cancer among young women (aged ≤40 years) has increased in North America and Europe. Fewer than 10% of cases among young women are attributable to inherited BRCA1 or BRCA2 mutations, suggesting an important role for somatic mutations. This study investigat...
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-020-6684-z |
| _version_ | 1828896123348058112 |
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| author | Nicole E. Mealey Dylan E. O’Sullivan Joy Pader Yibing Ruan Edwin Wang May Lynn Quan Darren R. Brenner |
| author_facet | Nicole E. Mealey Dylan E. O’Sullivan Joy Pader Yibing Ruan Edwin Wang May Lynn Quan Darren R. Brenner |
| author_sort | Nicole E. Mealey |
| collection | DOAJ |
| description | Abstract Background The incidence of breast cancer among young women (aged ≤40 years) has increased in North America and Europe. Fewer than 10% of cases among young women are attributable to inherited BRCA1 or BRCA2 mutations, suggesting an important role for somatic mutations. This study investigated genomic differences between young- and older-onset breast tumours. Methods In this study we characterized the mutational landscape of 89 young-onset breast tumours (≤40 years) and examined differences with 949 older-onset tumours (> 40 years) using data from The Cancer Genome Atlas. We examined mutated genes, mutational load, and types of mutations. We used complementary R packages “deconstructSigs” and “SomaticSignatures” to extract mutational signatures. A recursively partitioned mixture model was used to identify whether combinations of mutational signatures were related to age of onset. Results Older patients had a higher proportion of mutations in PIK3CA, CDH1, and MAP3K1 genes, while young-onset patients had a higher proportion of mutations in GATA3 and CTNNB1. Mutational load was lower for young-onset tumours, and a higher proportion of these mutations were C > A mutations, but a lower proportion were C > T mutations compared to older-onset tumours. The most common mutational signatures identified in both age groups were signatures 1 and 3 from the COSMIC database. Signatures resembling COSMIC signatures 2 and 13 were observed among both age groups. We identified a class of tumours with a unique combination of signatures that may be associated with young age of onset. Conclusions The results of this exploratory study provide some evidence that the mutational landscape and mutational signatures among young-onset breast cancer are different from those of older-onset patients. The characterization of young-onset tumours could provide clues to their etiology which may inform future prevention. Further studies are required to confirm our findings. |
| first_indexed | 2024-12-13T14:38:05Z |
| format | Article |
| id | doaj.art-d037f8aeb89841fa9db81570dda5abb3 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-13T14:38:05Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-d037f8aeb89841fa9db81570dda5abb32022-12-21T23:41:40ZengBMCBMC Cancer1471-24072020-03-0120111810.1186/s12885-020-6684-zMutational landscape differences between young-onset and older-onset breast cancer patientsNicole E. Mealey0Dylan E. O’Sullivan1Joy Pader2Yibing Ruan3Edwin Wang4May Lynn Quan5Darren R. Brenner6Department of Oncology, Cumming School of Medicine, University of CalgaryDepartment of Public Health Sciences, Queen’s UniversityDepartment of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health ServicesDepartment of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health ServicesDepartment of Biochemistry & Molecular Biology, Cumming School of Medicine, University of CalgaryDepartment of Oncology, Cumming School of Medicine, University of CalgaryDepartment of Oncology, Cumming School of Medicine, University of CalgaryAbstract Background The incidence of breast cancer among young women (aged ≤40 years) has increased in North America and Europe. Fewer than 10% of cases among young women are attributable to inherited BRCA1 or BRCA2 mutations, suggesting an important role for somatic mutations. This study investigated genomic differences between young- and older-onset breast tumours. Methods In this study we characterized the mutational landscape of 89 young-onset breast tumours (≤40 years) and examined differences with 949 older-onset tumours (> 40 years) using data from The Cancer Genome Atlas. We examined mutated genes, mutational load, and types of mutations. We used complementary R packages “deconstructSigs” and “SomaticSignatures” to extract mutational signatures. A recursively partitioned mixture model was used to identify whether combinations of mutational signatures were related to age of onset. Results Older patients had a higher proportion of mutations in PIK3CA, CDH1, and MAP3K1 genes, while young-onset patients had a higher proportion of mutations in GATA3 and CTNNB1. Mutational load was lower for young-onset tumours, and a higher proportion of these mutations were C > A mutations, but a lower proportion were C > T mutations compared to older-onset tumours. The most common mutational signatures identified in both age groups were signatures 1 and 3 from the COSMIC database. Signatures resembling COSMIC signatures 2 and 13 were observed among both age groups. We identified a class of tumours with a unique combination of signatures that may be associated with young age of onset. Conclusions The results of this exploratory study provide some evidence that the mutational landscape and mutational signatures among young-onset breast cancer are different from those of older-onset patients. The characterization of young-onset tumours could provide clues to their etiology which may inform future prevention. Further studies are required to confirm our findings.http://link.springer.com/article/10.1186/s12885-020-6684-zMutational signaturesBreast cancerYoung womenGenomicsSomatic mutations |
| spellingShingle | Nicole E. Mealey Dylan E. O’Sullivan Joy Pader Yibing Ruan Edwin Wang May Lynn Quan Darren R. Brenner Mutational landscape differences between young-onset and older-onset breast cancer patients BMC Cancer Mutational signatures Breast cancer Young women Genomics Somatic mutations |
| title | Mutational landscape differences between young-onset and older-onset breast cancer patients |
| title_full | Mutational landscape differences between young-onset and older-onset breast cancer patients |
| title_fullStr | Mutational landscape differences between young-onset and older-onset breast cancer patients |
| title_full_unstemmed | Mutational landscape differences between young-onset and older-onset breast cancer patients |
| title_short | Mutational landscape differences between young-onset and older-onset breast cancer patients |
| title_sort | mutational landscape differences between young onset and older onset breast cancer patients |
| topic | Mutational signatures Breast cancer Young women Genomics Somatic mutations |
| url | http://link.springer.com/article/10.1186/s12885-020-6684-z |
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