So far, no clear histopathological and molecular features of breast tumours occurring in ATM deleterious variant carriers have been described, but identification of an ATM-associated tumour signature may help in patient management.
The analysis of additional breast tumors from ten BC families in which a germline ATM mutation had been identified revealed a high frequency of wild-type allele loss.
We used qRT-PCR assay to quantify mRNA levels of ATM gene in 454 breast tumours from patients with known clinical/pathological status and outcome; reverse phase protein arrays (RPPA) were used to assess the levels of ATM and 14 proteins in 233 breast tumours.
Analysis of loss of heterozygosity (LOH) in 18 breast tumors from women carrying likely pathogenic rare sequence variants revealed no consistent pattern of loss of the ATM variant.
We have found that carriers of an ATM missense mutation, who were treated with radiotherapy for the first breast tumour, developed their second tumour on average in a 92-month interval compared to a 136-month mean interval for those CBC patients who neither received RT nor carried a germline variant, (p = 0.029).
To investigate whether aberrant methylation of the ATM promoter or loss of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) may be the underlying causes of reduced ATM protein levels often seen in breast tumours.
Fifty-two breast tumors from 51 patients, 38 of them with concomitant in situ component (CIS), were analyzed by immunohistochemistry for the expression of ATM.