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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 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.

SUBMITTER: Mealey NE

PROVIDER: S-EPMC7068998 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Mutational landscape differences between young-onset and older-onset breast cancer patients.

Mealey Nicole E NE O'Sullivan Dylan E DE Pader Joy J Ruan Yibing Y Wang Edwin E Quan May Lynn ML Brenner Darren R DR

BMC cancer 20200312 1

<h4>Background</h4>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.<h4>Methods</h4>In this study we characterized the mutational landscape of 89 young-onset breast tumours (≤40 years) and examined di ...[more]

PMID: 32164620

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Mutational landscape differences between young-onset and older-onset breast cancer patients.

Publications

Mutational landscape differences between young-onset and older-onset breast cancer patients.

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