Evidence map›Paper›PMID 34986841›Full record

ArticleBMC cancer2022

The clinical significance of adenomatous polyposis coli (APC) and catenin Beta 1 (CTNNB1) genetic aberrations in patients with melanoma.

Georgia Sofia Karachaliou, Rached Alkallas, Sarah B Carroll, Chongshan Caressi, Danny Zakria, Nirali M Patel, Dimitri G Trembath, Jennifer A Ezzell, Guillaume J Pegna, Paul B Googe and 10 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.7field-weighted citation impact, top 29% of its field
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

8 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Review
  3. Melanoma genomics - will we go beyond BRAF in clinics?Journal of cancer research and clinical oncology · 2024
    Review
  4. Article
  5. Article
  6. Article
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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

20 authors at 4 institutions in 2 countries.

Georgia Sofia KarachaliouDepartment of Medicine, The University of North Carolina at Chapel Chapel Hill, Chapel Hill, NC, USA.
Rached AlkallasDepartment of Biochemistry, McGill University, Montreal, QC, Canada.
Sarah B CarrollDepartment of Medicine, The University of North Carolina at Chapel Chapel Hill, Chapel Hill, NC, USA.
Chongshan CaressiCalifornia Pacific Medical Center Research Institute, San Francisco, CA, USA.
Danny ZakriaDepartment of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Nirali M PatelDepartment of Pathology & Laboratory Medicine, The University of North Carolina at Chapel Chapel Hill, Chapel Hill, NC, USA.
Dimitri G TrembathDepartment of Pathology & Laboratory Medicine, The University of North Carolina at Chapel Chapel Hill, Chapel Hill, NC, USA.
Jennifer A EzzellDepartment of Cell Biology & Physiology, Histology Research Core Facility, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Guillaume J PegnaDepartment of Medicine, The University of North Carolina at Chapel Chapel Hill, Chapel Hill, NC, USA.
Paul B GoogeDepartment of Dermatology, The University of North Carolina at Chapel Chapel Hill, Chapel Hill, NC, USA.
Jonathan P GaleottiDepartment of Pathology & Laboratory Medicine, The University of North Carolina at Chapel Chapel Hill, Chapel Hill, NC, USA.
Fatih AyvaliDepartment of Medicine, The University of North Carolina at Chapel Chapel Hill, Chapel Hill, NC, USA.
Frances A CollichioDepartment of Medicine, The University of North Carolina at Chapel Chapel Hill, Chapel Hill, NC, USA.
Carrie B LeeDepartment of Medicine, The University of North Carolina at Chapel Chapel Hill, Chapel Hill, NC, USA.
David W OllilaLineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Margaret L GulleyDepartment of Pathology & Laboratory Medicine, The University of North Carolina at Chapel Chapel Hill, Chapel Hill, NC, USA.
Douglas B JohnsonDepartment of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Kevin B KimCalifornia Pacific Medical Center Research Institute, San Francisco, CA, USA.
Ian R WatsonDepartment of Biochemistry, McGill University, Montreal, QC, Canada.
Stergios J MoschosDepartment of Medicine, The University of North Carolina at Chapel Chapel Hill, Chapel Hill, NC, USA. moschos@med.unc.edu.
University of North Carolina at Chapel Hill · USCalifornia Pacific Medical Center · USMcGill University · CAVanderbilt University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMelanoma-intrinsic activated β-catenin pathway, the product of the catenin beta 1 (CTNNB1) gene, has been associated with low/absent tumor-infiltrating lymphocytes, accelerated tumor growth, metastases development, and resistance to anti-PD-L1/anti-CTLA-4 agents in mouse melanoma models. Little is known about the association between the adenomatous polyposis coli (APC) and CTNNB1 gene mutations in stage IV melanoma with immunotherapy response and overall survival (OS).

methodsWe examined the prognostic significance of somatic APC/CTNNB1 mutations in the Cancer Genome Atlas Project for Skin Cutaneous Melanoma (TCGA-SKCM) database. We assessed APC/CTNNB1 mutations as predictors of response to immunotherapies in a clinicopathologically annotated metastatic patient cohort from three US melanoma centers.

resultsIn the TCGA-SKCM patient cohort (n = 434) presence of a somatic APC/CTNNB1 mutation was associated with a worse outcome only in stage IV melanoma (n = 82, median OS of APC/CTNNB1 mutants vs. wild-type was 8.15 vs. 22.8 months; log-rank hazard ratio 4.20, p = 0.011). APC/CTNNB1 mutation did not significantly affect lymphocyte distribution and density. In the 3-melanoma institution cohort, tumor tissues underwent targeted panel sequencing using two standards of care assays. We identified 55 patients with stage IV melanoma and APC/CTNNB1 genetic aberrations (mut) and 169 patients without (wt). At a median follow-up of more than 25 months for both groups, mut compared with wt patients had slightly more frequent (44% vs. 39%) and earlier (66% vs. 45% within six months from original diagnosis of stage IV melanoma) development of brain metastases. Nevertheless, time-to-development of brain metastases was not significantly different between the two groups. Fortunately, mut patients had similar clinical benefits from PD-1 inhibitor-based treatments compared to wt patients (median OS 26.1 months vs. 29.9 months, respectively, log-rank p = 0.23). Less frequent mutations in the NF1, RAC1, and PTEN genes were seen in the mut compared with wt patients from the 3-melanoma institution cohort. Analysis of brain melanoma tumor tissues from a separate craniotomy patient cohort (n = 55) showed that melanoma-specific, activated β-catenin (i.e., nuclear localization) was infrequent (n = 3, 6%) and not prognostic in established brain metastases.

conclusionsAPC/CTNNB1 mutations are associated with a worse outcome in stage IV melanoma and early brain metastases independent of tumor-infiltrating lymphocyte density. However, PD1 inhibitor-based treatments provide comparable benefits to both mut and wt patients with stage IV melanoma.

Indexed as

Genes, APCAdultAgedAged, 80 and overbeta CateninCutaneous Malignant MelanomaFemaleHumansLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedMutationNeoplasm StagingPrognosisProportional Hazards Modelsbeta CateninCTNNB1 protein, humanCentral nervous system neoplasmsGenetic markersImmunomodulationImmunotherapyMelanoma

Identifiers

PMID34986841
PMCPMC8734243
OpenAlexW4206306245

What OpenQuestion holds

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LicenceCC BY
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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.