Evidence mapPaperPMID 41524698Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2026

Integrative Clinical and Molecular Evaluation of Renal Cell Carcinoma with Merlin Protein Deficiency and Biallelic Loss of NF2.

Emre Yekedüz, Weiwei Bian, Stephanie E Siegmund, Marc Machaalani, Jad El Masri, Mustafa Saleh, Eddy Saad, Liliana Ascione, Razane El Hajj Chehade, Clara Steiner and 9 more

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. 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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

19 authors.

Emre YekedüzLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-6819-5930
Weiwei BianLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-1536-2947
Stephanie E SiegmundHarvard Medical School, Boston, Massachusetts.ORCID 0000-0003-1848-2389
Marc MachaalaniLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-6708-9922
Jad El MasriLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-6991-2508
Mustafa SalehLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-2757-113X
Eddy SaadLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-8700-9312
Liliana AscioneLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-2807-7400
Razane El Hajj ChehadeLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0007-3424-6585
Clara SteinerLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0008-8640-1636
Pablo Moura BarriosLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0006-6250-787X
Stephanie A BergLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-6193-5350
Bradley McGregorLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-8298-0289
Charlene MantiaLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-7672-3131
Praful RaviLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-7466-4702
Wenxin XuLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-8450-2037
Michelle S HirschHarvard Medical School, Boston, Massachusetts.ORCID 0000-0002-8767-8564
Toni K ChoueiriLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-9201-3217
Michael SerzanLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-6453-8035

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI Geoffrey I. Shapiro · 1985 to 2026
$330.6M
Treating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WILLIAM G. KAELIN, David McDermott · 2003 to 2026
$53.4M
Dana-Farber/Harvard Cancer Center (DF/HCC) Program 5P30CA006516-56Dana-Farber/Harvard Cancer Center (DF/HCC) SPORE (2P50CA101942-16)NCI NIH HHS P30 CA006516NCI NIH HHS P50 CA101942
6 · The paper itself

Abstract

purposeIn renal cell carcinoma (RCC), loss of the NF2 tumor suppressor gene encoding the merlin protein is associated with aggressive clinical behavior. However, data about the clinical course and additional molecular features in the context of contemporary systemic therapies remain limited. EXPERIMENTAL

designClinical outcomes were evaluated in patients with RCC exhibiting merlin loss by IHC in one academic cohort. Integrative genomic analyses were performed, including targeted DNA sequencing via the institutional OncoPanel assay and RNA sequencing data from The Cancer Genome Atlas (TCGA).

resultsIn the institutional cohort (n = 33), most patients had biphasic hyalinizing psammomatous RCC (66.6%) and metastatic disease (78.8%). Among 23 patients receiving systemic therapy, those treated with non-immunotherapy (IO)-based regimens (n = 5) had numerically longer overall survival (24.5 vs. 16.5 months, P = 0.2) and progression-free survival (9.8 vs. 5 months, P = 0.5) compared with IO-based therapies (n = 18) though differences were not statistically significant. Genomic analysis (n = 17) revealed frequent truncating mutations of NF2 (82.3%) and recurrent alterations in chromatin remodeling and DNA damage-response signaling genes with prominent deletions in tumor suppressor genes such as CDKN2A/B. Transcriptomic profiling of NF2-inactivated tumors from TCGA (n = 13) demonstrated enrichment of cellular proliferation and concurrent suppression of metabolic and immune pathways, suggesting an aggressive phenotype compared with clear-cell RCC without NF2 inactivation (n = 529).

conclusionsBiallelic NF2 inactivation and merlin protein deficiency drive an aggressive RCC phenotype marked by immune dysfunction, high proliferation, and frequent cell cycle and DNA damage-response signaling alterations. Limited treatment response to IO highlights the need for molecularly tailored therapies.

Indexed as

Biomarkers, TumorCarcinoma, Renal CellKidney NeoplasmsNeurofibromin 2AdultAgedAllelesFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedMutationPrognosisBiomarkers, TumorNeurofibromin 2NF2 protein, human

Identifiers

PMID41524698
PMCPMC12924687

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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.