Evidence map›Paper›PMID 28539123›Full record

ArticleGenome medicine2017

Multilevel genomics of colorectal cancers with microsatellite instability-clinical impact of JAK1 mutations and consensus molecular subtype 1.

Anita Sveen, Bjarne Johannessen, Torstein Tengs, Stine A Danielsen, Ina A Eilertsen, Guro E Lind, Kaja C G Berg, Edward Leithe, Leonardo A Meza-Zepeda, Enric Domingo and 6 more

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

Article in Genome medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
8.5field-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.

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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.

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  18. Transcriptomic Profiling of MSI-H/dMMR Gastrointestinal Tumors to Identify Determinants of Responsiveness to Anti-PD-1 Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 2 countries.

Anita SveenDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, P.O. Box 4953, Nydalen, NO-0424, Oslo, Norway.
Bjarne JohannessenDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, P.O. Box 4953, Nydalen, NO-0424, Oslo, Norway.
Torstein TengsDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, P.O. Box 4953, Nydalen, NO-0424, Oslo, Norway.
Stine A DanielsenDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, P.O. Box 4953, Nydalen, NO-0424, Oslo, Norway.
Ina A EilertsenDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, P.O. Box 4953, Nydalen, NO-0424, Oslo, Norway.
Guro E LindDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, P.O. Box 4953, Nydalen, NO-0424, Oslo, Norway.
Kaja C G BergDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, P.O. Box 4953, Nydalen, NO-0424, Oslo, Norway.
Edward LeitheDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, P.O. Box 4953, Nydalen, NO-0424, Oslo, Norway.
Leonardo A Meza-ZepedaNorwegian Cancer Genomics Consortium, Oslo University Hospital, P.O. Box 4953, Nydalen, NO-0424, Oslo, Norway.
Enric DomingoWellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
Ola MyklebostNorwegian Cancer Genomics Consortium, Oslo University Hospital, P.O. Box 4953, Nydalen, NO-0424, Oslo, Norway.
David KerrDepartment of Oncology, University of Oxford, Roosevelt Drive, Oxford, OX3 7DQ, UK.
Ian TomlinsonWellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
Arild NesbakkenK. G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, P.O. Box 4953, Nydalen, NO-0424, Oslo, Norway.
Rolf I SkotheimDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, P.O. Box 4953, Nydalen, NO-0424, Oslo, Norway.
Ragnhild A LotheDepartment of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, P.O. Box 4953, Nydalen, NO-0424, Oslo, Norway. rlothe@rr-research.no.
University of Oslo · NOOslo University Hospital · NOCentre for Human Genetics · GBOslo Cancer Cluster · NOUniversity of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundApproximately 15% of primary colorectal cancers have DNA mismatch repair deficiency, causing a complex genome with thousands of small mutations-the microsatellite instability (MSI) phenotype. We investigated molecular heterogeneity and tumor immunogenicity in relation to clinical endpoints within this distinct subtype of colorectal cancers.

methodsA total of 333 primary MSI+ colorectal tumors from multiple cohorts were analyzed by multilevel genomics and computational modeling-including mutation profiling, clonality modeling, and neoantigen prediction in a subset of the tumors, as well as gene expression profiling for consensus molecular subtypes (CMS) and immune cell infiltration.

resultsNovel, frequent frameshift mutations in four cancer-critical genes were identified by deep exome sequencing, including in CRTC1, BCL9, JAK1, and PTCH1. JAK1 loss-of-function mutations were validated with an overall frequency of 20% in Norwegian and British patients, and mutated tumors had up-regulation of transcriptional signatures associated with resistance to anti-PD-1 treatment. Clonality analyses revealed a high level of intra-tumor heterogeneity; however, this was not associated with disease progression. Among the MSI+ tumors, the total mutation load correlated with the number of predicted neoantigens (P = 4 × 10

conclusionsMultilevel genomic analyses of MSI+ colorectal cancer revealed molecular heterogeneity with clinical relevance, including tumor immunogenicity and a favorable patient outcome associated with JAK1 mutations and the transcriptomic subgroup CMS1, emphasizing the potential for prognostic stratification of this clinically important subtype. See related research highlight by Samstein and Chan 10.1186/s13073-017-0438-9.

Indexed as

Microsatellite InstabilityMutationAdultAgedAged, 80 and overColorectal NeoplasmsDNA Mutational AnalysisFemaleGene Expression ProfilingGenomicsHumansJanus Kinase 1MaleMiddle AgedJAK1 protein, humanJanus Kinase 1Colorectal cancerConsensus molecular subtypesImmunogenicityImmunotherapy resistanceJAK1Microsatellite instabilityMutationNeoantigenPrognosis

Identifiers

PMID28539123
PMCPMC5442873
OpenAlexW2618584226

What OpenQuestion holds

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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.