Evidence map›Paper›PMID 22536370›Full record

ArticlePloS one2012

Routine multiplex mutational profiling of melanomas enables enrollment in genotype-driven therapeutic trials.

Christine M Lovly, Kimberly Brown Dahlman, Laurel E Fohn, Zengliu Su, Dora Dias-Santagata, Donna J Hicks, Donald Hucks, Elizabeth Berry, Charles Terry, MarKeesa Duke and 8 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05501912 (A Phase I, Open-Label, Multicenter, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-Cancer Activity of ABM-1310 in Patients With BRAF V600-Mutant Advanced Solid Tumors), which is not on this map. Cited by 105 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 3 pooled it
11.3field-weighted citation impact, top 1% 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.

NCT05501912 phase1terminatednot on this mapstarted 2022, after this paper: background citation

A Phase I, Open-Label, Multicenter, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-Cancer Activity of ABM-1310 in Patients With BRAF V600-Mutant Advanced Solid Tumors

TypeinterventionalSponsorABM Therapeutics Shanghai Company LimitedRan2022 to 2024Enrolled20ConditionsAdvanced Solid Tumor, BRAF V600 MutationArmsABM-1310
3 · Its place in the literature

Who cites it

105 citing papers in PubMed, 3 syntheses or guidelines pooled it, 202 citations in OpenAlex.

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  4. Longitudinal Genomic Analysis to Fine-tune Targeted Therapy: Results of the Phase II LOGIC 2 Trial in Patients with BRAFV600-Mutant Metastatic Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
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45 more citing papers are in PubMed but not listed here.

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

18 authors at 4 institutions in 1 country.

Christine M LovlyDivision of Hematology-Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Kimberly Brown Dahlman
Laurel E Fohn
Zengliu Su
Dora Dias-Santagata
Donna J Hicks
Donald Hucks
Elizabeth Berry
Charles Terry
MarKeesa Duke
Yingjun Su
Tammy Sobolik-Delmaire
Ann Richmond
Mark C Kelley
Cindy L Vnencak-Jones
A John Iafrate
Jeffrey Sosman
William Pao
Vanderbilt University · USVanderbilt University Medical Center · USHarvard University · USMassachusetts General Hospital · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
TrainingU54CA163072 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Karen Marie Winkfield · 2011 to 2026
$20.1M
Targeting the NF-kappaB Pathway in MelanomaR01CA116021 · NCI · VANDERBILT UNIVERSITY · PI RICHMOND, ANN, YAN, CHI · 2005 to 2024
$6.7M
The Vanderbilt Institute for Clinical and Translational Research (VICTR) KL2KL2RR024977 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$3.0M
Clinical Investigation in Tumor ImmunotherapyK24CA097588 · NCI · VANDERBILT UNIVERSITY · PI SOSMAN, JEFFREY A · 2002 to 2012
$1.5M
The Vanderbilt Institute for Clinical and Translational Research (VICTR) TL1TL1RR024978 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$1.3M
BLRD VA IK6 BX005225NCI NIH HHS 5K24 CA97588-06NCI NIH HHS CA68485NCI NIH HHS K24 CA097588NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA116021NCI NIH HHS U54 CA163072NCRR NIH HHS KL2 RR024977NCRR NIH HHS TL1 RR024978NCRR NIH HHS UL1 RR024975NCRR NIH HHS UL1 RR024975-01
6 · The paper itself

Abstract

purposeKnowledge of tumor mutation status is becoming increasingly important for the treatment of cancer, as mutation-specific inhibitors are being developed for clinical use that target only sub-populations of patients with particular tumor genotypes. Melanoma provides a recent example of this paradigm. We report here development, validation, and implementation of an assay designed to simultaneously detect 43 common somatic point mutations in 6 genes (BRAF, NRAS, KIT, GNAQ, GNA11, and CTNNB1) potentially relevant to existing and emerging targeted therapies specifically in melanoma.

methodsThe test utilizes the SNaPshot method (multiplex PCR, multiplex primer extension, and capillary electrophoresis) and can be performed rapidly with high sensitivity (requiring 5-10% mutant allele frequency) and minimal amounts of DNA (10-20 nanograms). The assay was validated using cell lines, fresh-frozen tissue, and formalin-fixed paraffin embedded tissue. Clinical characteristics and the impact on clinical trial enrollment were then assessed for the first 150 melanoma patients whose tumors were genotyped in the Vanderbilt molecular diagnostics lab.

resultsDirecting this test to a single disease, 90 of 150 (60%) melanomas from sites throughout the body harbored a mutation tested, including 57, 23, 6, 3, and 2 mutations in BRAF, NRAS, GNAQ, KIT, and CTNNB1, respectively. Among BRAF V600 mutations, 79%, 12%, 5%, and 4% were V600E, V600K, V600R, and V600M, respectively. 23 of 54 (43%) patients with mutation harboring metastatic disease were subsequently enrolled in genotype-driven trials.

conclusionWe present development of a simple mutational profiling screen for clinically relevant mutations in melanoma. Adoption of this genetically-informed approach to the treatment of melanoma has already had an impact on clinical trial enrollment and prioritization of therapy for patients with the disease.

Indexed as

Eligibility DeterminationGenetic TestingCell Line, TumorClinical Trials as TopicDNA Mutational AnalysisGTP-Binding Protein alpha SubunitsGTP-Binding Protein alpha Subunits, Gq-G11HumansMaleMelanomaMolecular Diagnostic TechniquesNerve Tissue ProteinsPoint MutationProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-kitProto-Oncogene Proteins p21(ras)BRAF protein, humanGNA11 protein, humanGNAQ protein, humanGTP-Binding Protein alpha SubunitsGTP-Binding Protein alpha Subunits, Gq-G11Nerve Tissue ProteinsProto-Oncogene Proteins B-rafProto-Oncogene Proteins c-kitProto-Oncogene Proteins p21(ras)SHANK2 protein, human

Identifiers

PMID22536370
PMCPMC3335021
OpenAlexW2125333956

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Registered trials

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.