Abstract
IntroductionFamilial breast cancer (fBC) is generally associated with an early age of diagnosis and a higher frequency of disease among family members. Over the past two decades a number of genes have been identified that are unequivocally associated with breast cancer (BC) risk but there remain a significant proportion of families that cannot be accounted for by these genes. Copy number variants (CNVs) are a form of genetic variation yet to be fully explored for their contribution to fBC. CNVs exert their effects by either being associated with whole or partial gene deletions or duplications and by interrupting epigenetic patterning thereby contributing to disease development. CNV analysis can also be used to identify new genes and loci which may be associated with disease risk.MethodsThe Affymetrix Cytogenetic Whole Genome 2.7 M (Cyto2.7 M) arrays were used to detect regions of genomic re-arrangement in a cohort of 129 fBC BRCA1/BRCA2 mutation negative patients with a young age of diagnosis (<50 years) compared to 40 unaffected healthy controls (>55 years of age).ResultsCNV analysis revealed the presence of 275 unique rearrangements that were not present in the control population suggestive of their involvement in BC risk. Several CNVs were found that have been previously reported as BC susceptibility genes. This included CNVs in RPA3, NBN (NBS1), MRE11A and CYP19A1 in five unrelated fBC patients suggesting that these genes are involved in BC initiation and/or progression. Of special interest was the identification of WWOX and FHIT rearrangements in three unrelated fBC patients.ConclusionsThis study has identified a number of CNVs that potentially contribute to BC initiation and/or progression. The identification of CNVs that are associated with known tumour suppressor genes is of special interest that warrants further larger studies to understand their precise role in fBC.
Highlights
Familial breast cancer is generally associated with an early age of diagnosis and a higher frequency of disease among family members
This study has identified a number of Copy Number Variants (CNV) that potentially contribute to breast cancer (BC) initiation and/or progression
The identification of CNVs that are associated with known tumour suppressor genes is of special interest that warrants further larger studies to understand their precise role in Familial breast cancer (fBC)
Summary
Familial breast cancer (fBC) is generally associated with an early age of diagnosis and a higher frequency of disease among family members. CNVs exert their effects by either being associated with whole or partial gene deletions or duplications and by interrupting epigenetic patterning thereby contributing to disease development. CNV analysis can be used to identify new genes and loci which may be associated with disease risk. Two reports have recently examined CNVs in association with BRCA1/BRCA2 mutation negative fBC patients The first of these has reported a greater abundance of rare CNVs in fBC patients and suggest that rare CNVs are likely to contain genetic factors associated with BC predisposition, while the second report associated several CNV markers with fBC risk and suggests their use in disease risk assessment [24,25]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
