Evidence map›Paper›PMID 41417427›Full record

ArticleMolecular biology reports2025

Ultra-deep targeted next-generation sequencing with peripheral blood in patients with vascular malformations: a cohort of 40 patients.

Shintaro Mitamura, Kosuke Ishikawa, Kanako C Hatanaka, Tatsuro Saito, Yuki Sasaki, Takahiro Miura, Taku Maeda, Emi Funayama, Naoki Murao, Satoru Sasaki and 1 more

Abstract read
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In one paragraph

Article in Molecular biology reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

11 authors.

Shintaro MitamuraFaculty of Medicine and Graduate School of Medicine, Department of Plastic and Reconstructive Surgery, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.ORCID http://orcid.org/0009-0006-5131-1038
Kosuke IshikawaFaculty of Medicine and Graduate School of Medicine, Department of Plastic and Reconstructive Surgery, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. kishikawa-hok@umin.ac.jp.ORCID http://orcid.org/0000-0002-6068-7276
Kanako C HatanakaCenter for Development of Advanced Diagnostics, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, Japan.
Tatsuro SaitoResearch Division of Genome Companion Diagnostics, Hokkaido University Hospital, Sapporo, Japan.
Yuki SasakiFaculty of Medicine and Graduate School of Medicine, Department of Plastic and Reconstructive Surgery, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.ORCID http://orcid.org/0000-0002-1953-4366
Takahiro MiuraFaculty of Medicine and Graduate School of Medicine, Department of Plastic and Reconstructive Surgery, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.ORCID http://orcid.org/0000-0003-4180-6556
Taku MaedaFaculty of Medicine and Graduate School of Medicine, Department of Plastic and Reconstructive Surgery, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.ORCID http://orcid.org/0000-0003-3612-8201
Emi FunayamaFaculty of Medicine and Graduate School of Medicine, Department of Plastic and Reconstructive Surgery, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Naoki MuraoCenter for Vascular Anomalies, Department of Plastic and Reconstructive Surgery, Tonan Hospital, Sapporo, Japan.
Satoru SasakiCenter for Vascular Anomalies, Department of Plastic and Reconstructive Surgery, Tonan Hospital, Sapporo, Japan.
Yutaka HatanakaCenter for Development of Advanced Diagnostics, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, Japan.ORCID http://orcid.org/0000-0003-3128-1477

Funding

Japan Society for the Promotion of Science JP23K09072
6 · The paper itself

Abstract

backgroundVascular malformations originate from congenital abnormalities in vascular differentiation and formation, and their subtypes exhibit diverse overlapping phenotypes that make differential diagnosis challenging. Recent advances in next-generation sequencing (NGS) technology for tissue specimens have enabled the identification of somatic variants in genes that are associated with vascular malformations, such as those in the RAS/MEK/ERK and phosphoinositide 3-kinase/AKT/mTOR pathways. Liquid biopsy using cell-free DNA (cfDNA) is a minimally invasive alternative method that has recently been applied to vascular malformations. This study aimed to apply ultra-deep targeted NGS using liquid biopsy to detect somatic variants in vascular malformations.

methodsA total of 10 mL peripheral blood was collected from 40 patients with vascular malformations, and cfDNA was extracted for liquid biopsy. Ultra-deep NGS (mean coverage: 104,000×) with unique molecular identifier error correction was performed using a custom panel of five genes: BRAF, KRAS, MAP2K1, PIK3CA, and TEK/TIE2.

resultsThe diagnoses included arteriovenous malformation (AVM, n = 11), PIK3CA-related overgrowth spectrum (PROS, n = 9), and venous malformation (VM, n = 20). Somatic variants were identified in 23 patients, even at a low variant allele frequency of 0.05%. Hotspot BRAF and KRAS variants and a non-hotspot MAP2K1 variant were detected in patients with AVM. Fifteen variants were detected in seven patients with PROS, including hotspot PIK3CA variants in helical domains. Three novel PIK3CA and four novel TEK variants were identified in patients with VM.

conclusionsLiquid biopsy of cfDNA from the peripheral blood enables safe, outpatient-compatible molecular diagnosis, to potentially guide tailored treatment.

Indexed as

High-Throughput Nucleotide SequencingVascular MalformationsAdolescentAdultArteriovenous MalformationsCell-Free Nucleic AcidsChildChild, PreschoolClass I Phosphatidylinositol 3-KinasesCohort StudiesFemaleHumansInfantLiquid BiopsyMaleMAP Kinase Kinase 1BRAF protein, humanCell-Free Nucleic AcidsClass I Phosphatidylinositol 3-KinasesKRAS protein, humanMAP2K1 protein, humanMAP Kinase Kinase 1PIK3CA protein, humanProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)Receptor, TIE-2TEK protein, humanArteriovenous malformationBRAFCell-free DNAKRASLiquid biopsyMAP2K1PIK3CAPIK3CA-related overgrowth spectrumTEK TIE2Venous malformation

Identifiers

PMID41417427

What Socratic holds

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Registered trials

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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 Socratic graph.