Evidence map›Paper›PMID 40866717›Full record

Observational studyJournal of cancer research and clinical oncology2025

Clinicopathological and genomic analysis of SWI/SNF chromatin remodeling abnormalities with a focus on SMARCA4 in cancer of unknown primary.

Yasutaka Tono, Koshi Sukeno, Akira Tsunoda, Mariko Okayama, Hiroki Oka, Hiroyasu Oda, Kanako Saito, Yoshiki Yamashita, Masayasu Taniguchi, Makoto Ikejiri and 5 more

Abstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Journal of cancer research and clinical oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

15 authors.

Yasutaka TonoDepartment of Medical Oncology, Mie University Hospital, 2-174, Tsu, 514- 8507, Mie, Japan. ytono@med.mie-u.ac.jp.
Koshi SukenoDepartment of Medical Oncology, Mie University Hospital, 2-174, Tsu, 514- 8507, Mie, Japan.
Akira TsunodaDepartment of Medical Oncology, Mie University Hospital, 2-174, Tsu, 514- 8507, Mie, Japan.
Mariko OkayamaDepartment of Medical Oncology, Ise Red Cross Hospital, Mie, 516-8512, Ise, Japan.
Hiroki OkaDepartment of Medical Oncology, Mie University Hospital, 2-174, Tsu, 514- 8507, Mie, Japan.
Hiroyasu OdaDepartment of Medical Oncology, Ise Red Cross Hospital, Mie, 516-8512, Ise, Japan.
Kanako SaitoDepartment of Medical Oncology, Mie University Hospital, 2-174, Tsu, 514- 8507, Mie, Japan.
Yoshiki YamashitaDepartment of Medical Oncology, Mie University Hospital, 2-174, Tsu, 514- 8507, Mie, Japan.
Masayasu TaniguchiDepartment of Medical Oncology, Ise Red Cross Hospital, Mie, 516-8512, Ise, Japan.
Makoto IkejiriDepartment of Clinical Laboratory, Mie University Hospital, Tsu, 514-8507, Japan.
Satoshi TamaruClinical Research Support Center, Mie University Hospital, Tsu, 514-8507, Japan.
Masaki TanabeDepartment of Clinical Laboratory, Mie University Hospital, Tsu, 514-8507, Japan.
Hiroshi ImaiPathology Division, Mie University Hospital, Tsu, 514-8507, Mie, Japan.
Masatoshi WatanabeDepartment of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, 514-8507, Mie, Japan.
Toshiro MizunoDepartment of Medical Oncology, Mie University Hospital, 2-174, Tsu, 514- 8507, Mie, Japan.

Funding

EKIDEN FOR LIFE N/A
6 · The paper itself

Abstract

purposeThe estimation of the primary site is crucial when considering chemotherapy regimens in cancer of unknown primary (CUP). The task is particularly challenging for poorly differentiated or undifferentiated carcinoma, or unknown histological tumors with unknown primary (U-CUP). Instead of site-specific chemotherapy, a biomarker-guided therapy using genomic testing is required to predict the efficacy of molecular-targeted agents and immune checkpoint inhibitors (ICI). We focused on inactivating the SWI/SNF complex, a chromatin regulatory complex. We investigated the clinical features of CUP with SWI/SNF chromatin remodeling abnormalities and examined whether SWI/SNF chromatin remodeling abnormalities are a predictive marker of ICI efficacy.

methodsA multi-institutional observational study was conducted between January 2009 and March 2022. Immunostaining for SMARCA2, SMARCA4, and SMARCB1 was performed on 80 patients with CUP. Nextgeneration sequencing analysis was conducted on SMARCA4, SMARCA2, SMARCB1, ARID1A, PBRM1, ARID2, and ARID1B, which are frequent SWI/SNF-associated genes, in 32 patients with CUP.

resultsImmunohistochemistry revealed that the loss of SMARCA4 protein was most frequent, occurring in 14 patients (17.5%). Among the 32 patients with CUP, SMARCA4 mutations were detected in 50% (n = 16) of patients. In 6 cases with truncating mutations, immunostaining revealed protein loss. U-CUP cases were associated with loss of SMARCA4 protein. In SMARCA4-deficient patients, overall survival was prolonged in the ICI-containing regimen group (p = 0.033).

conclusionThis study demonstrated SWI/SNF chromatin remodeling abnormalities in CUP and the association between SMARCA4 deficiency and U-CUP. It suggests a potential strategy for selecting an ICI regimen for CUP, particularly U-CUP, with SMARCA4 deficiency.

Indexed as

Biomarkers, TumorChromatin Assembly and DisassemblyDNA HelicasesNeoplasms, Unknown PrimaryNuclear ProteinsTranscription FactorsAdultAgedAged, 80 and overChromosomal Proteins, Non-HistoneDNA-Binding ProteinsFemaleGenomicsHumansImmune Checkpoint InhibitorsMaleARID1B protein, humanBiomarkers, TumorChromosomal Proteins, Non-HistoneDNA-Binding ProteinsDNA HelicasesImmune Checkpoint InhibitorsNuclear ProteinsSMARCA2 protein, humanSMARCA4 protein, humanSMARCB1 ProteinSMARCB1 protein, humanTranscription FactorsCancer of unknown primaryChromatin remodelingSMARCA4SWI/SNF

Identifiers

PMID40866717
PMCPMC12390907

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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 OpenQuestion graph.