BRCA1 gene promoter methylation status in high-grade serous ovarian cancer patients - A study of the tumour Bank ovarian cancer (TOC) and ovarian cancer diagnosis consortium (OVCAD)

I Ruscito; D Dimitrova; I Vasconcelos; K Gellhaus; T Schwachula; F Bellati; R Zeillinger; P Benedetti-Panici; I Vergote; S Mahner; D Cacsire-Tong; N Concin; S Darb-Esfahani; S Lambrechts; J Sehouli; S Olek; E I Braicu

doi:10.1016/j.ejca.2014.05.001

BRCA1 gene promoter methylation status in high-grade serous ovarian cancer patients - A study of the tumour Bank ovarian cancer (TOC) and ovarian cancer diagnosis consortium (OVCAD)

Standard

BRCA1 gene promoter methylation status in high-grade serous ovarian cancer patients - A study of the tumour Bank ovarian cancer (TOC) and ovarian cancer diagnosis consortium (OVCAD). / Ruscito, I; Dimitrova, D; Vasconcelos, I; Gellhaus, K; Schwachula, T; Bellati, F; Zeillinger, R; Benedetti-Panici, P; Vergote, I; Mahner, S; Cacsire-Tong, D; Concin, N; Darb-Esfahani, S; Lambrechts, S; Sehouli, J; Olek, S; Braicu, E I.

In: EUR J CANCER, Vol. 50, No. 12, 01.08.2014, p. 2090-2098.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Ruscito, I, Dimitrova, D, Vasconcelos, I, Gellhaus, K, Schwachula, T, Bellati, F, Zeillinger, R, Benedetti-Panici, P, Vergote, I, Mahner, S, Cacsire-Tong, D, Concin, N, Darb-Esfahani, S, Lambrechts, S, Sehouli, J, Olek, S & Braicu, EI 2014, 'BRCA1 gene promoter methylation status in high-grade serous ovarian cancer patients - A study of the tumour Bank ovarian cancer (TOC) and ovarian cancer diagnosis consortium (OVCAD)', EUR J CANCER, vol. 50, no. 12, pp. 2090-2098. https://doi.org/10.1016/j.ejca.2014.05.001

APA

Ruscito, I., Dimitrova, D., Vasconcelos, I., Gellhaus, K., Schwachula, T., Bellati, F., Zeillinger, R., Benedetti-Panici, P., Vergote, I., Mahner, S., Cacsire-Tong, D., Concin, N., Darb-Esfahani, S., Lambrechts, S., Sehouli, J., Olek, S., & Braicu, E. I. (2014). BRCA1 gene promoter methylation status in high-grade serous ovarian cancer patients - A study of the tumour Bank ovarian cancer (TOC) and ovarian cancer diagnosis consortium (OVCAD). EUR J CANCER, 50(12), 2090-2098. https://doi.org/10.1016/j.ejca.2014.05.001

Vancouver

Ruscito I, Dimitrova D, Vasconcelos I, Gellhaus K, Schwachula T, Bellati F et al. BRCA1 gene promoter methylation status in high-grade serous ovarian cancer patients - A study of the tumour Bank ovarian cancer (TOC) and ovarian cancer diagnosis consortium (OVCAD). EUR J CANCER. 2014 Aug 1;50(12):2090-2098. https://doi.org/10.1016/j.ejca.2014.05.001

Bibtex

@article{7c9c9180a0e343988ee83cb162135bf3,

title = "BRCA1 gene promoter methylation status in high-grade serous ovarian cancer patients - A study of the tumour Bank ovarian cancer (TOC) and ovarian cancer diagnosis consortium (OVCAD)",

abstract = "BACKGROUND: Mutations in BRCA1/2 genes are involved in the pathogenesis of breast and ovarian cancer. Inactivation of these genes can also be mediated by hypermethylation of CpGs in the promoter regions. Aim of this study was to analyse the clinical impact of BRCA1 promoter gene methylation status in a homogenous cohort of high-grade serous ovarian cancer (HGSOC) patients.METHODS: The cohort included 257 primary HGSOC patients treated by cytoreduction and platinum-based chemotherapy. DNA was extracted from fresh frozen tissue samples. BRCA1 gene promoter methylation rate was assessed using polymerase chain reaction (PCR).RESULTS: 14.8% of patients presented hypermethylation within a selected region of the BRCA1 promoter. The rate of hypermethylation was significantly higher in younger patients (20.8% hypermethylation in the age group ⩽58years versus 8.7% hypermethylation in the age group >58years; p=0.008). Optimal tumour debulking could be reached in 63% of patients, without significant differences in the extent of residual disease with respect to the methylation status. No impact of BRCA1 gene promoter methylation status on progression free- and overall-survival rates was found. No significant differences within BRCA1 promoter methylation status between primary and metastatic tissue could be observed. These results on BRCA1 promoter methylation status were also confirmed in a subgroup of 107 patients found negative for BRCA1 exon 11 mutations.CONCLUSIONS: Our data suggest that BRCA1 methylation determines the earlier onset of HGSOC. Furthermore our study supports the idea that BRCAness is not only due to mutations but also to epigenetic changes in BRCA1 promoter gene.",

author = "I Ruscito and D Dimitrova and I Vasconcelos and K Gellhaus and T Schwachula and F Bellati and R Zeillinger and P Benedetti-Panici and I Vergote and S Mahner and D Cacsire-Tong and N Concin and S Darb-Esfahani and S Lambrechts and J Sehouli and S Olek and Braicu, {E I}",

year = "2014",

month = aug,

day = "1",

doi = "10.1016/j.ejca.2014.05.001",

language = "English",

volume = "50",

pages = "2090--2098",

journal = "EUR J CANCER",

issn = "0959-8049",

publisher = "Elsevier Limited",

number = "12",

}

RIS

TY - JOUR

T1 - BRCA1 gene promoter methylation status in high-grade serous ovarian cancer patients - A study of the tumour Bank ovarian cancer (TOC) and ovarian cancer diagnosis consortium (OVCAD)

AU - Ruscito, I

AU - Dimitrova, D

AU - Vasconcelos, I

AU - Gellhaus, K

AU - Schwachula, T

AU - Bellati, F

AU - Zeillinger, R

AU - Benedetti-Panici, P

AU - Vergote, I

AU - Mahner, S

AU - Cacsire-Tong, D

AU - Concin, N

AU - Darb-Esfahani, S

AU - Lambrechts, S

AU - Sehouli, J

AU - Olek, S

AU - Braicu, E I

PY - 2014/8/1

Y1 - 2014/8/1

N2 - BACKGROUND: Mutations in BRCA1/2 genes are involved in the pathogenesis of breast and ovarian cancer. Inactivation of these genes can also be mediated by hypermethylation of CpGs in the promoter regions. Aim of this study was to analyse the clinical impact of BRCA1 promoter gene methylation status in a homogenous cohort of high-grade serous ovarian cancer (HGSOC) patients.METHODS: The cohort included 257 primary HGSOC patients treated by cytoreduction and platinum-based chemotherapy. DNA was extracted from fresh frozen tissue samples. BRCA1 gene promoter methylation rate was assessed using polymerase chain reaction (PCR).RESULTS: 14.8% of patients presented hypermethylation within a selected region of the BRCA1 promoter. The rate of hypermethylation was significantly higher in younger patients (20.8% hypermethylation in the age group ⩽58years versus 8.7% hypermethylation in the age group >58years; p=0.008). Optimal tumour debulking could be reached in 63% of patients, without significant differences in the extent of residual disease with respect to the methylation status. No impact of BRCA1 gene promoter methylation status on progression free- and overall-survival rates was found. No significant differences within BRCA1 promoter methylation status between primary and metastatic tissue could be observed. These results on BRCA1 promoter methylation status were also confirmed in a subgroup of 107 patients found negative for BRCA1 exon 11 mutations.CONCLUSIONS: Our data suggest that BRCA1 methylation determines the earlier onset of HGSOC. Furthermore our study supports the idea that BRCAness is not only due to mutations but also to epigenetic changes in BRCA1 promoter gene.

AB - BACKGROUND: Mutations in BRCA1/2 genes are involved in the pathogenesis of breast and ovarian cancer. Inactivation of these genes can also be mediated by hypermethylation of CpGs in the promoter regions. Aim of this study was to analyse the clinical impact of BRCA1 promoter gene methylation status in a homogenous cohort of high-grade serous ovarian cancer (HGSOC) patients.METHODS: The cohort included 257 primary HGSOC patients treated by cytoreduction and platinum-based chemotherapy. DNA was extracted from fresh frozen tissue samples. BRCA1 gene promoter methylation rate was assessed using polymerase chain reaction (PCR).RESULTS: 14.8% of patients presented hypermethylation within a selected region of the BRCA1 promoter. The rate of hypermethylation was significantly higher in younger patients (20.8% hypermethylation in the age group ⩽58years versus 8.7% hypermethylation in the age group >58years; p=0.008). Optimal tumour debulking could be reached in 63% of patients, without significant differences in the extent of residual disease with respect to the methylation status. No impact of BRCA1 gene promoter methylation status on progression free- and overall-survival rates was found. No significant differences within BRCA1 promoter methylation status between primary and metastatic tissue could be observed. These results on BRCA1 promoter methylation status were also confirmed in a subgroup of 107 patients found negative for BRCA1 exon 11 mutations.CONCLUSIONS: Our data suggest that BRCA1 methylation determines the earlier onset of HGSOC. Furthermore our study supports the idea that BRCAness is not only due to mutations but also to epigenetic changes in BRCA1 promoter gene.

U2 - 10.1016/j.ejca.2014.05.001

DO - 10.1016/j.ejca.2014.05.001

M3 - SCORING: Journal article

C2 - 24889916

VL - 50

SP - 2090

EP - 2098

JO - EUR J CANCER

JF - EUR J CANCER

SN - 0959-8049

IS - 12

ER -