Evidence map›Paper›PMID 30204251›Full record

ArticleCancer2018

GNAS, GNAQ, and GNA11 alterations in patients with diverse cancers.

Austin J Parish, Vi Nguyen, Aaron M Goodman, Karthikeyan Murugesan, Garrett M Frampton, Razelle Kurzrock

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
1.5field-weighted citation impact, top 20% 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

36 citing papers in PubMed, 47 citations in OpenAlex.

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  16. Discovery of small molecule GActa pharmaceutica Sinica. B · 2022
    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

6 authors at 2 institutions in 3 countries.

Austin J ParishCenter for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, Louisiana Jolla, California.
Vi NguyenCenter for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, Louisiana Jolla, California.
Aaron M GoodmanCenter for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, Louisiana Jolla, California.
Karthikeyan MurugesanFoundation Medicine, Inc, Cambridge, Massachusetts.
Garrett M FramptonFoundation Medicine, Inc, Cambridge, Massachusetts.
Razelle KurzrockCenter for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, Louisiana Jolla, California.ORCID 0000-0003-4110-1214
University of California San Diego · USPHG Foundation · GB

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
Joan and Irwin Jacobs FundNCI NIH HHS P30 CA016672NCI NIH HHS P30 CA023100
6 · The paper itself

Abstract

backgroundAdvances in deep sequencing technology have uncovered a widespread, protumorigenic role of guanine nucleotide-binding (G protein) α (GNA) subunits, particularly GNA subunits Gs (GNAS), Gq (GNAQ), and G11 (GNA11) (GNA*), in a diverse collection of malignancies. The objectives of the current study were: 1) to determine GNA* aberration status in a cohort of 1348 patients with cancer and 2) to examine tumor mutational burden, overall survival rates, and treatment outcomes in patients with GNA*-positive tumors versus those with tumors that had wild-type GNA*.

methodsFor each patient, clinical and genomic data were collected from medical records. Next-generation sequencing was performed for each patient (range, 182-236 genes).

resultsAberrations of GNA* genes were identified in a subset of patients who had 8 of the 12 cancer types examined, and a significant association was observed for appendiceal cancer and ocular melanoma (P < .0001 for both; multivariate analysis). Overall, 4.1% of the cancer population was affected. GNA* abnormalities were associated with higher numbers of co-alterations in univariate (but not multivariate) analysis and were most commonly accompanied by Aurora kinase A (AURKA), Cbl proto-oncogene (CBL), and LYN proto-oncogene (LYN) co-alterations (all P < .0001; multivariate analysis). GNA* alterations were correlated with a trend toward lower median overall survival (P = .085). The median tumor mutational burden was 4 mutations per megabase in both GNA*-altered and GNA* wild-type tumors. For this limited sample of GNA*-positive patients, longer survival was not correlated with any specific treatment regimens.

conclusionsIn the current sample, the genes GNAS, GNAQ, and GNA11 were widely altered across cancer types, and these alterations often were accompanied by specific genomic abnormalities in AURKA, CBL, and LYN. Therefore, targeting GNA* alterations may require drugs that address the GNA* signal and important co-alterations. Cancer 2018;00:000-000. © 2018 American Cancer Society.

Indexed as

AdolescentAdultAgedAged, 80 and overChildChild, PreschoolChromograninsCohort StudiesDNA Mutational AnalysisFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGTP-Binding Protein alpha SubunitsGTP-Binding Protein alpha Subunits, Gq-G11GTP-Binding Protein alpha Subunits, GsHigh-Throughput Nucleotide SequencingChromograninsGNA11 protein, humanGNAQ protein, humanGNAS protein, humanGTP-Binding Protein alpha SubunitsGTP-Binding Protein alpha Subunits, Gq-G11GTP-Binding Protein alpha Subunits, GsMAS1 protein, humanProto-Oncogene Masdeep sequencingG-proteinguanine nucleotide-binding protein G(q) subunit α (GNAQ)guanine nucleotide-binding protein G(s) subunit α (GNAS)guanine nucleotide-binding protein G subunit α11 (GNA11)mutation burden

Identifiers

PMID30204251
PMCPMC6234097
OpenAlexW2890148776

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.