Evidence map›Paper›PMID 31483290›Full record

ArticleThe Journal of clinical investigation2019

Genetic hallmarks of recurrent/metastatic adenoid cystic carcinoma.

Allen S Ho, Angelica Ochoa, Gowtham Jayakumaran, Ahmet Zehir, Cristina Valero Mayor, Justin Tepe, Vladimir Makarov, Martin G Dalin, Jie He, Mark Bailey and 19 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 1 pooled it
20.3field-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.

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

124 citing papers in PubMed, 1 synthesis or guideline pooled it, 201 citations in OpenAlex.

  1. Deciphering NOTCH1 as a Biomarker in Adenoid Cystic Carcinoma: Insights From a Systematic Review With Meta-Analysis.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2025
    Pooled it
  2. TROP2 Expression in Salivary Gland Adenoid Cystic Carcinoma (ACC) According to Histologic Subtype: Therapeutic Implications.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2025
    Trial
  3. Phase 2 Trial of Regorafenib in Recurrent/Metastatic Adenoid Cystic Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Trial
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  12. Renaissance of farnesyltransferase inhibitors in cancer.Journal of translational medicine · 2026
    Review
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64 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

29 authors at 10 institutions in 2 countries.

Allen S HoDepartment of Surgery and.
Angelica OchoaMarie-Josée and Henry R. Kravis Center for Molecular Oncology.
Gowtham JayakumaranDiagnostic Molecular Pathology.
Ahmet ZehirDiagnostic Molecular Pathology.
Cristina Valero MayorHead and Neck Service, Department of Surgery, and.
Justin TepeHead and Neck Service, Department of Surgery, and.
Vladimir MakarovHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, New York, USA.
Martin G DalinHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, New York, USA.
Jie HeFoundation Medicine, Cambridge, Massachusetts, USA.
Mark BaileyFoundation Medicine, Cambridge, Massachusetts, USA.
Meagan MontesionFoundation Medicine, Cambridge, Massachusetts, USA.
Jeffrey S RossFoundation Medicine, Cambridge, Massachusetts, USA.
Vincent A MillerFoundation Medicine, Cambridge, Massachusetts, USA.
Lindsay ChanFoundation Medicine, Cambridge, Massachusetts, USA.
Ian GanlyHead and Neck Service, Department of Surgery, and.
Snjezana DoganDiagnostic Molecular Pathology.
Nora KatabiDiagnostic Molecular Pathology.
Petros TsipourasDepartment of Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
Patrick HaDepartment of Otolaryngology-Head and Neck Surgery, UCSF, San Francisco, California, USA.
Nishant AgrawalDepartment of Surgery, University of Chicago, Chicago, Illinois, USA.
David B SolitMarie-Josée and Henry R. Kravis Center for Molecular Oncology.
P Andrew FutrealDepartment of Genomic Medicine and.
Adel K El NaggarDepartment of Pathology, University of Texas MD Anderson Cancer Center (MDACC), Houston, Texas, USA.
Jorge S Reis-FilhoExperimental Pathology Service, MSKCC, New York, New York, USA.
Britta WeigeltExperimental Pathology Service, MSKCC, New York, New York, USA.
Alan L HoDepartment of Medicine.
Nikolaus SchultzMarie-Josée and Henry R. Kravis Center for Molecular Oncology.
Timothy A ChanHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, New York, USA.
Luc Gt MorrisHead and Neck Service, Department of Surgery, and.
Foundation Medicine (United States)Memorial Sloan Kettering Cancer Center · USDNA Diagnostic (Denmark) · DKCedars-Sinai Medical Center · USManhattan Scientifics (United States) · USMolecular Oncology (United States) · USThe University of Texas MD Anderson Cancer Center · USUniversity of California, San Francisco · USUniversity of Chicago · USYale University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
TOWARDS PRECISION IMMUNO-ONCOLOGY: UNRAVELING THE GENOMIC DETERMINANTS AND MECHANISMS UNDERLYING IMMUNOTHERAPY EFFICACY AND RESISTANCER35CA232097 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI CHAN, TIMOTHY AN-THY · 2018 to 2024
$7.0M
Elucidating genetics of response to immune checkpoint blockade in lung cancerR01CA205426 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CHAN, TIMOTHY AN-THY, RIZVI, NAIYER A · 2017 to 2021
$3.2M
Identifying and targeting neoantigens in aggressive salivary carcinomasR01DE027738 · NIDCR · SLOAN-KETTERING INST CAN RESEARCH · PI CHAN, TIMOTHY AN-THY, HO, ALAN L. · 2018 to 2022
$2.8M
Functionalizing recurrent FAT1 mutations and deletions in oral cancerK08DE024774 · NIDCR · SLOAN-KETTERING INST CAN RESEARCH · PI MORRIS, LUC GORDON TRANG · 2014 to 2018
$682k
NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA205426NCI NIH HHS R35 CA232097NIDCR NIH HHS K08 DE024774NIDCR NIH HHS R01 DE027738
6 · The paper itself

Abstract

BACKGROUNDAdenoid cystic carcinoma (ACC) is a rare malignancy arising in salivary glands and other sites, characterized by high rates of relapse and distant spread. Recurrent/metastatic (R/M) ACCs are generally incurable, due to a lack of active systemic therapies. To improve outcomes, deeper understanding of genetic alterations and vulnerabilities in R/M tumors is needed.METHODSAn integrated genomic analysis of 1,045 ACCs (177 primary, 868 R/M) was performed to identify alterations associated with advanced and metastatic tumors. Intratumoral genetic heterogeneity, germline mutations, and therapeutic actionability were assessed.RESULTSCompared with primary tumors, R/M tumors were enriched for alterations in key Notch (NOTCH1, 26.3% vs. 8.5%; NOTCH2, 4.6% vs. 2.3%; NOTCH3, 5.7% vs. 2.3%; NOTCH4, 3.6% vs. 0.6%) and chromatin-remodeling (KDM6A, 15.2% vs. 3.4%; KMT2C/MLL3, 14.3% vs. 4.0%; ARID1B, 14.1% vs. 4.0%) genes. TERT promoter mutations (13.1% of R/M cases) were mutually exclusive with both NOTCH1 mutations (q = 3.3 × 10-4) and MYB/MYBL1 fusions (q = 5.6 × 10-3), suggesting discrete, alternative mechanisms of tumorigenesis. This network of alterations defined 4 distinct ACC subgroups: MYB+NOTCH1+, MYB+/other, MYBWTNOTCH1+, and MYBWTTERT+. Despite low mutational load, we identified numerous samples with marked intratumoral genetic heterogeneity, including branching evolution across multiregion sequencing.CONCLUSIONThese observations collectively redefine the molecular underpinnings of ACC progression and identify further targets for precision therapies.FUNDINGAdenoid Cystic Carcinoma Research Foundation, Pershing Square Sohn Cancer Research grant, the PaineWebber Chair, Stand Up 2 Cancer, NIH R01 CA205426, the STARR Cancer Consortium, NCI R35 CA232097, the Frederick Adler Chair, Cycle for Survival, the Jayme Flowers Fund, The Sebastian Nativo Fund, NIH K08 DE024774 and R01 DE027738, and MSKCC through NIH/NCI Cancer Center Support Grant (P30 CA008748).

Indexed as

MutationAdultCarcinoma, Adenoid CysticChromatin Assembly and DisassemblyFemaleGenes, mybGenomicsHumansMaleMiddle AgedNeoplasm Recurrence, LocalReceptors, NotchSalivary Gland NeoplasmsTelomeraseReceptors, NotchTelomeraseTERT protein, humanHead and neck cancerOncology

Identifiers

PMID31483290
PMCPMC6763222
OpenAlexW2971684115

What OpenQuestion holds

Textmetadata
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.