Highlights
- •HER2 overexpression is more common in proline carriers of the Ala1170Pro SNP.
- •Heterozygosity in HER2 SNPs was lost in more than 80% of HER2-positive tumours.
- •Normal breast tissue retained the HER2 germline genotype in all but one case.
Abstract
Human epidermal growth factor receptor 2 (HER2) overexpression in breast cancer is
an indicator of poor prognosis and is the pre-requisite for treatment with the agents
targeting this member of the epidermal growth factor receptor family. In order to
determine the influence of these common single-nucleotide polymorphisms (SNPs) in
the HER2 gene, genomic DNA was obtained from 361 patients with breast cancer, aged between
29 and 82 years. Samples of tumour tissue were obtained from 241 (66%) patients and
material for extraction of DNA is isolated from surrounding normal tissue by laser
capture microdissection. Genotyping was performed using the Taqman fluorogenic 5′ nuclease assay. Of the 360 patients with definitive determination
of HER2 status, 49% were positive. The Ile655Val SNP had no influence on the frequency
of HER2 expression. However, the proline allele of the Ala1170Pro SNP was associated
with a higher frequency of HER2 overexpression (56% versus 43%, p = 0.015). Where
the germline genotype was homozygous, the tumour genotype was identical in every case
and for both SNPs. In HER2-positive tumours, heterozygosity was maintained in only
15% and 18% of the Ile655Val and Ala1170Pro SNPs, respectively. This was lower than
in the HER2-negative tumours (46% and 43%, respectively). Normal breast tissue (n = 23)
retained the germline genotype in all but one case. The underlying link between the
Ala1170Pro SNP and HER2 positivity is not known, nor is the significance of HER2 overexpression
and loss of heterozygosity in breast cancer. However, these results illustrate the
complexity of HER2 genotype and overexpression in this disease.
Keywords
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Article info
Publication history
Published online: January 07, 2016
Accepted:
October 26,
2015
Received in revised form:
August 5,
2015
Received:
April 20,
2015
Identification
Copyright
© 2015 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
