Evidence map›Paper›PMID 39549430›Full record

ArticleOral oncology2024

Long read sequencing identifies complex structural variant landscape and recurrent TERT rearrangements in mucoepidermoid carcinoma.

Elizabeth Gensterblum-Miller, Apurva Bhangale, Dana Al Majid, Victor Murcia Pienkowski, Malgorzata Rydzanicz, Joanna Janiszewska, Magdalena Kostrzewska-Poczekaj, Clifford Chang, Collin Brummel, Nicole L Michmerhuizen and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oral oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. The Molecular Biology of MEC Salivary Gland Tumors.Annals of otolaryngology and rhinology · 2025
    Article
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

21 authors.

Elizabeth Gensterblum-MillerDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA; Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, USA.
Apurva BhangaleDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
Dana Al MajidDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
Victor Murcia PienkowskiDepartment of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
Malgorzata RydzaniczDepartment of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.
Joanna JaniszewskaInstitute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Magdalena Kostrzewska-PoczekajInstitute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Clifford ChangDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
Collin BrummelDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
Nicole L MichmerhuizenDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA; Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Jiayu WangDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA; Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Erin SandfordDepartment of Int Med-Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA.
Muneesh TewariDepartment of Int Med-Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Malgorzata WierzbickaInstitute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Andrew C BirkelandDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
Jonathan B McHughDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Matthew E SpectorDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Maciej GiefingInstitute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Malgorzata Jarmuz-SzymczakInstitute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Molly E Heft NealDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
J Chad BrennerDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA; Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, USA; Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA. Electronic address: chadbren@umich.edu.

Funding

Dissecting Co-Dependent Pathways in Oral CancersU01DE025184 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BRENNER, JOHN CHADWICK, CAREY, THOMAS E. · 2015 to 2018
$3.7M
Advanced Research Training in OtolaryngologyT32DC005356 · NIDCD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CORFAS, GABRIEL · 2002 to 2021
$3.5M
Analysis of the E7-Mediated Mechanism of MHC Class I Repression in HNSCCF31DE030000 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GENSTERBLUM-MILLER, ELIZABETH · 2020 to 2022
$114k
NIDCD NIH HHS T32 DC005356NIDCR NIH HHS F31 DE030000NIDCR NIH HHS U01 DE025184
6 · The paper itself

Abstract

Mucoepidermoid Carcinoma (MEC) is a common salivary malignant neoplasm. Approximately 60 % of MECs harbor translocations between CRTC1 or CRTC3 and MAML2, which are thought to drive disease pathogenesis. However, the precise structural mechanism driving this rearrangement remains uncharacterized. Here, we performed multi-omic and long read genomic sequencing, discovering a chain of alterations that created the CRTC1::MAML2 fusion, but also an unexpected MAML2 to MYBL1 rearrangement, suggesting that MYBL1 may play a larger role in salivary gland cancers than previously recognized. Furthermore, we discovered and validated recurrent TERT rearrangements and amplifications in MEC models. 5/5 MEC cell lines and 36/39 (92 %) primary MEC tumors harbored a TERT rearrangement or copy number amplification. Custom sequencing of the TERT locus confirmed translocation breakpoints in 13/33 (39 %) MECs, while exome sequencing confirmed frequent TERT amplifications. Critically, TERT knockdown in NCI-H292, a cell line with TERT promoter rearrangement, reduced clonogenic cell survival, supporting a critical role of this gene in MEC tumorigenesis. Overall, our data suggest that complex chromothripsis rearrangement mechanisms drive the formation of structural variation in CRTC1::MAML2 fusion positive and negative tumors and reveal highly recurrent structural variation driving TERT rearrangement in MEC.

Indexed as

Carcinoma, MucoepidermoidGene RearrangementTelomeraseCell Line, TumorDNA-Binding ProteinsFemaleHumansMaleOncogene Proteins, FusionProto-Oncogene ProteinsSalivary Gland NeoplasmsTrans-ActivatorsTranscription FactorsTranslocation, GeneticCRTC1 protein, humanDNA-Binding ProteinsMAML2 protein, humanMYBL1 protein, humanOncogene Proteins, FusionProto-Oncogene ProteinsTelomeraseTERT protein, humanTrans-ActivatorsTranscription FactorsCRTC1MAML2MECNOTCH2Structural variationTERTTranslocation

Identifiers

PMID39549430
PMCPMC11983472

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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.