Recurrent copy number alterations in young women with breast cancer.

Chen Chi,Pingzhao Hu,Leigh C Murphy

doi:10.18632/oncotarget.24336

Abstract

Breast cancer diagnosis in young women has emerged as an independent prognostic factor with higher recurrence risk and death than their older counterparts. We aim to find recurrent somatic copy number alteration (CNA) regions identified from breast cancer microarray data and associate the CNA status of the genes harbored in the regions to the survival of young women with breast cancer.By using the interval graph-based algorithm we developed, and the CNA data consisting of a Discovery set with 130 young women and a Validation set with 125 young women, we identified 38 validated recurrent CNAs containing 39 protein encoding genes. CNA gain regions encompassing genes CAPN2, CDC73 and ASB13 are the top 3 with the highest occurring frequencies in both the Discovery and Validation dataset, while gene SGCZ ranked top for the recurrent CNA loss regions. The mutation status of 9 of the 39 genes shows significant associations with breast cancer specific survival. Interestingly, the expression level of 2 of the 9 genes, ASB13 and SGCZ, shows significant association with survival outcome. Patients with CNA mutations in both of these genes had a worse survival outcome when compared to patients without the gene mutations. The mutated CNA status in gene ASB13 was associated with a higher gene expression, which predicted patient survival outcome. Together, identification of the CNA events with prognostic significance in young women with breast cancer may be used in genomic-guided treatment.

Highlights

Young women only account for 7% of all breast cancers, it is the most common cancer among young females [1]
By using the interval graph-based algorithm we developed, and the copy number alteration (CNA) data consisting of a Discovery set with 130 young women and a Validation set with 125 young women, we identified validated recurrent CNAs containing protein encoding genes
Applying the graph-based algorithm to the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) breast cancer dataset, we have identified and validated 81 recurrent CNA gain regions and 25 validated recurrent CNA loss regions specific to young-Women's breast cancers

Summary

Introduction

Young women only account for 7% of all breast cancers, it is the most common cancer among young females [1]. Young age at diagnosis of breast cancer has emerged as an independent factor for higher recurrence risk and death in various studies [2,3,4,5,6]. Several factors influence poor prognosis in the young subgroup, such as higher tumour grade at diagnosis, high tumour proliferation, increased expression of HER-2 (ERB-B2) and reduced expression of both estrogen (ER) and progesterone receptor (PR) [7]. These women often struggle with life issues that are either absent or much less severe in older women, such as the possibility of early menopause and effects on fertility. While clinicopathologic differences point to underlying biological differences between breast tumours found in younger versus older women, limited studies have documented age-related changes at the molecular level

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