The Association between Mutational Signatures and Clinical Outcomes among Patients with Early-Onset Breast Cancer.

Autor:	Basmadjian RB; Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 4Z6, Canada., O'Sullivan DE; Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 4Z6, Canada.; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada.; Department of Cancer Epidemiology and Prevention Research, Cancer Research and Analytics, Cancer Care Alberta, Alberta Health Services, Calgary, AB T2S 3C3, Canada., Quan ML; Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 4Z6, Canada.; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada.; Department of Surgery, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 2T9, Canada., Lupichuk S; Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 4Z6, Canada.; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada., Xu Y; Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 4Z6, Canada.; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada.; Department of Surgery, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 2T9, Canada., Cheung WY; Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 4Z6, Canada.; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada., Brenner DR; Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 4Z6, Canada.; Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada.
Jazyk:	angličtina
Zdroj:	Genes [Genes (Basel)] 2024 May 07; Vol. 15 (5). Date of Electronic Publication: 2024 May 07.
DOI:	10.3390/genes15050592
Abstrakt:	Early-onset breast cancer (EoBC), defined by a diagnosis <40 years of age, is associated with poor prognosis. This study investigated the mutational landscape of non-metastatic EoBC and the prognostic relevance of mutational signatures using 100 tumour samples from Alberta, Canada. The MutationalPatterns package in R/Bioconductor was used to extract de novo single-base substitution (SBS) and insertion-deletion (indel) mutational signatures and to fit COSMIC SBS and indel signatures. We assessed associations between these signatures and clinical characteristics of disease, in addition to recurrence-free (RFS) and overall survival (OS). Five SBS and two indel signatures were extracted. The SBS13-like signature had higher relative contributions in the HER2-enriched subtype. Patients with higher than median contribution tended to have better RFS after adjustment for other prognostic factors (HR = 0.29; 95% CI: 0.08-1.06). An unsupervised clustering algorithm based on absolute contribution revealed three clusters of fitted COSMIC SBS signatures, but cluster membership was not associated with clinical variables or survival outcomes. The results of this exploratory study reveal various SBS and indel signatures may be associated with clinical features of disease and prognosis. Future studies with larger samples are required to better understand the mechanistic underpinnings of disease progression and treatment response in EoBC.
Databáze:	MEDLINE
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