However, the proline allele of the Ala1170ProSNPwas associated with a higher
frequency of HER2 overexpression (56% versus 43%, p Z 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 Z 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.
ª 2015 Elsevier Ltd. All rights reserved.
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