BRCA1 promoter hypermethylation on circulating tumor DNA correlates with improved survival of patients with ovarian cancer

被引：14

作者：

Elazezy, Maha ^{[1
]}

Prieske, Katharina ^{[2
,3
]}

Kluwe, Lan ^{[4
]}

Oliveira-Ferrer, Leticia ^{[2
]}

Peine, Sven ^{[5
]}

Mueller, Volkmar ^{[2
]}

Woelber, Linn ^{[2
]}

Schmalfeldt, Barbara ^{[2
]}

Pantel, Klaus ^{[1
]}

Joosse, Simon A. ^{[1
,3
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Dept Tumor Biol, Martinistr 52, D-20246 Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Dept Gynecol & Gynecol Oncol, Hamburg, Germany

[3] Univ Med Ctr Hamburg Eppendorf, Mildred Scheel Canc Career Ctr HaTriCS4, Hamburg, Germany

[4] Univ Med Ctr Hamburg Eppendorf, Dept Oral & Maxillofacial Surg, Hamburg, Germany

[5] Univ Med Ctr Hamburg Eppendorf, Dept Transfus Med, Hamburg, Germany

来源：

MOLECULAR ONCOLOGY | 2021年 / 15卷 / 12期

关键词：

BRCA1; ctDNA; liquid biopsy; MS-qPCR; SPORADIC BREAST; LIQUID BIOPSY; METHYLATION; QUANTIFICATION; FREQUENCY; MUTATIONS; REGION; PLASMA;

D O I：

10.1002/1878-0261.13108

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Methylation of the BRCA1 promoter is an epigenetic gene expression regulator and is frequently observed in ovarian cancer; however, conversion of methylation status is thought to drive disease recurrence. Therefore, longitudinal monitoring of methylation status by liquid biopsy in cell-free DNA may be a predictive marker. In total, 135 plasma samples were collected from 69 ovarian cancer patients before and during systemic treatment. Our liquid biopsy assay could detect down to a single molecule of methylated DNA in a high background of normal DNA (0.03%) with perfect specificity in control samples. We found that 60% of the cancer patients exhibited BRCA1 promoter hypermethylation at one point, although 24% lost hypermethylation during treatment. Multivariate survival analyses indicate that relapses are independent events and that hypermethylation and methylation conversion are independently correlated to longer relapse-free survival. We present a highly sensitive and specific methylation-specific quantitative PCR-based liquid biopsy assay. BRCA1 promoter hypermethylation is frequently found in ovarian cancer and is often reversed upon recurrence, indicating the selection of therapy-resistant clones and unfavorable clinical outcome.

引用

页码：3615 / 3625

页数：11

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