Background: The etiology of breast cancer (BC) is multi-factorial. The mammary tissue is particularly exposed to oxidative stress because of specific hormone metabolism. This state can produce oxidized DNA lesions such as 8-hydroxyguanine (8-oxoG), physiologically removed by the base excision repair (BER) pathway. A reduction of activities and/or transcript dosage imbalance in the BER genes may have a role in BC predisposition. Methods: DNA and RNA from peripheral blood mononuclear cells (PBMC) of 63 BC and/or ovarian cancer (OC) patients, previously screened for BRCA1/BRCA2, were studied for MUTYH and OGG1 germline variants using dHPLC and sequencing; TaqMan assays were employed to test mRNA expression levels. Results: Forty-six patients presented with cancer family history, 28 of them showing vertical transmission of BC; 17 were BC/OC early onset without family history. No cases had a detectable pathogenic mutation in BRCA1/BRCA2 genes. Ten sequence variants were identified in MUTYH and OGG1. Importantly, 2/6 of MUTYH missense mutations were found in the same BC patient and not detected in 120 healty controls. Gene expression was analysed on 46 patients with available RNA and 40 healthy donors selected according to similar gender and age. The MUTYH gene showed reduced expression in BC patients with and without evidence of direct genetic transmission compared to OC patients. Conclusions: Overall, significant reduced expression was observed in patient vs control group (p < 0.05) only for MUYH gene. While not conclusive, this interesting finding suggests clinical criteria for MUTYHand OGG1-associated BC and OC phenotypes.
Molecular Analysis of Base Excision Repair (BER) Genes in Breast and Ovarian Cancer Patients
MOSCATELLO, CARMELO;FANTINI, FABIANA;DI NICOLA, MARTA;MORGANO, ANNALISA;ANTONUCCI, IVANA;DI GREGORIO, PATRIZIA;BATTISTA, Pasquale;CAMA, Alessandro;CURIA, Maria Cristina
2016-01-01
Abstract
Background: The etiology of breast cancer (BC) is multi-factorial. The mammary tissue is particularly exposed to oxidative stress because of specific hormone metabolism. This state can produce oxidized DNA lesions such as 8-hydroxyguanine (8-oxoG), physiologically removed by the base excision repair (BER) pathway. A reduction of activities and/or transcript dosage imbalance in the BER genes may have a role in BC predisposition. Methods: DNA and RNA from peripheral blood mononuclear cells (PBMC) of 63 BC and/or ovarian cancer (OC) patients, previously screened for BRCA1/BRCA2, were studied for MUTYH and OGG1 germline variants using dHPLC and sequencing; TaqMan assays were employed to test mRNA expression levels. Results: Forty-six patients presented with cancer family history, 28 of them showing vertical transmission of BC; 17 were BC/OC early onset without family history. No cases had a detectable pathogenic mutation in BRCA1/BRCA2 genes. Ten sequence variants were identified in MUTYH and OGG1. Importantly, 2/6 of MUTYH missense mutations were found in the same BC patient and not detected in 120 healty controls. Gene expression was analysed on 46 patients with available RNA and 40 healthy donors selected according to similar gender and age. The MUTYH gene showed reduced expression in BC patients with and without evidence of direct genetic transmission compared to OC patients. Conclusions: Overall, significant reduced expression was observed in patient vs control group (p < 0.05) only for MUYH gene. While not conclusive, this interesting finding suggests clinical criteria for MUTYHand OGG1-associated BC and OC phenotypes.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
