Evidence map›Paper›PMID 40202107›Full record

ArticleCancer science2025

BRCA1 Promoter Methylation in Ovarian Cancer: Clinical Relevance and a Novel Diagnostic Approach Using Fragment Analysis.

Saki Tsuchimochi, Yoko Yamamoto, Ayumi Taguchi, Masahito Kawazu, Kenbun Sone, Masako Ikemura, Kana Tamai, Shuhei Kitamura, Daisuke Yoshimoto, Sayuri Fukaya and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Saki TsuchimochiDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Yoko YamamotoDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Ayumi TaguchiDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.ORCID https://orcid.org/0000-0002-5491-3871
Masahito KawazuDivision of Cell Therapy, Chiba Cancer Center, Research Institute, Chiba, Japan.
Kenbun SoneDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Masako IkemuraDepartment of Pathology, The University of Tokyo, Tokyo, Japan.
Kana TamaiDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Shuhei KitamuraDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Daisuke YoshimotoDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Sayuri FukayaDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Aya IshizakaDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Anh Duong QuynhDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Akira NishijimaDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Yuichiro MiyamotoDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Mayuyo MoriDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Osamu HiraikeDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Kosei HasegawaDepartment of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan.ORCID https://orcid.org/0000-0002-1903-7001
Tetsuo UshikuDepartment of Pathology, The University of Tokyo, Tokyo, Japan.
Katsutoshi OdaDepartment of Clinical Genomics, The University of Tokyo, Tokyo, Japan.
Yasushi HirotaDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
Yutaka OsugaDepartment of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.

Funding

Japan Agency for Medical Research and Development 24wm0325057h9902Japan Agency for Medical Research and Development JP21km0908001Japan Society for the Promotion of Science 21H03074Japan Society for the Promotion of Science 24K02584
6 · The paper itself

Abstract

Homologous recombination deficiency (HRD) tests, including MyChoice CDx, are companion diagnostics for poly (ADP-ribose) polymerase (PARP) inhibitors. BRCA1 promoter hypermethylation, a major HRD cause, may correlate with poorer prognosis. This study aimed to develop a simple, accurate method for detecting BRCA1 promoter hypermethylation and elucidate the characteristics of such cases. BRCA1 promoter methylation was analyzed using bisulfite sequencing (BIS-seq) in high-grade serous ovarian carcinoma specimens. We developed a newly developed BRCA1 methylation assay, BRCA1-Fragment Analysis of Methylation (BRCA1-FAM), which combines restriction enzyme digestion with fragment analysis. The accuracy of this assay was compared to the results of BIS-seq. We evaluated the relationship between BRCA1 promoter hypermethylation and prognosis and examined its association with BRCA1 expression and loss of heterozygosity. BRCA1 mutations and promoter methylation were mutually exclusive in the analyzed cases, with methylation observed in 28.9% (22/76) of primary debulking surgery cases. The BRCA1-FAM showed high sensitivity (91.3%) and specificity (100%) for detecting BRCA1 promoter hypermethylation, comparable to BIS-seq. Cases with BRCA1 promoter hypermethylation had significantly poorer progression-free survival (log-rank test, p = 0.048). Among these cases, 86.4% displayed abnormal BRCA1 immunostaining, with lower frequencies of BRCA1 loss of heterozygosity compared to those of other groups. BRCA1 promoter hypermethylation is associated with poor prognosis, underscoring the importance of its identification for HRD stratification. BRCA1-FAM is a simple and highly accurate method for evaluating BRCA1 promoter methylation. This approach may potentially enhance the precision of personalized therapies for ovarian cancer.

Indexed as

BRCA1 ProteinDNA MethylationOvarian NeoplasmsPromoter Regions, GeneticAdultAgedBiomarkers, TumorClinical RelevanceFemaleHumansLoss of HeterozygosityMiddle AgedMutationPrognosisBiomarkers, TumorBRCA1 ProteinBRCA1 protein, humanBRCA1DNA fragmentationDNA methylationhomologous recombination deficiencyovarian cancer

Identifiers

PMID40202107
PMCPMC12210050

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.