Evidence map›Paper›PMID 34051734›Full record

ArticleBMC cancer2021

Genetic analysis of sinonasal undifferentiated carcinoma discovers recurrent SWI/SNF alterations and a novel PGAP3-SRPK1 fusion gene.

Molly E Heft Neal, Andrew C Birkeland, Apurva D Bhangale, Jingyi Zhai, Aditi Kulkarni, Susan K Foltin, Brittany M Jewell, Megan L Ludwig, Lisa Pinatti, Hui Jiang and 4 more

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

Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. 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

14 authors at 1 institution in 1 country.

Molly E Heft Neal *Department of Otolaryngology - Head and Neck Surgery, University of Michigan, 1150 E. Medical Center Dr., 9301B MSRB3, Ann Arbor, MI, 48109-0602, USA.
Andrew C Birkeland *Department of Otolaryngology - Head and Neck Surgery, University of Michigan, 1150 E. Medical Center Dr., 9301B MSRB3, Ann Arbor, MI, 48109-0602, USA.
Apurva D BhangaleDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, 1150 E. Medical Center Dr., 9301B MSRB3, Ann Arbor, MI, 48109-0602, USA.
Jingyi ZhaiDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Aditi KulkarniDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, 1150 E. Medical Center Dr., 9301B MSRB3, Ann Arbor, MI, 48109-0602, USA.
Susan K FoltinDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, 1150 E. Medical Center Dr., 9301B MSRB3, Ann Arbor, MI, 48109-0602, USA.
Brittany M JewellDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, 1150 E. Medical Center Dr., 9301B MSRB3, Ann Arbor, MI, 48109-0602, USA.
Megan L LudwigDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, 1150 E. Medical Center Dr., 9301B MSRB3, Ann Arbor, MI, 48109-0602, USA.
Lisa PinattiDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, 1150 E. Medical Center Dr., 9301B MSRB3, Ann Arbor, MI, 48109-0602, USA.
Hui JiangDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Jonathan B McHughRogel Cancer Center, University of Michigan Medical School, 1150 E. Medical Center Dr., 9301B MSRB3, Ann Arbor, MI, 48109-0602, USA.
Lawence MarentetteDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, 1150 E. Medical Center Dr., 9301B MSRB3, Ann Arbor, MI, 48109-0602, USA.
Erin L McKeanDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, 1150 E. Medical Center Dr., 9301B MSRB3, Ann Arbor, MI, 48109-0602, USA.
J Chad BrennerDepartment of Otolaryngology - Head and Neck Surgery, University of Michigan, 1150 E. Medical Center Dr., 9301B MSRB3, Ann Arbor, MI, 48109-0602, USA. chadbren@umich.edu.
University of Michigan–Ann Arbor · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSinonasal Undifferentiated Carcinoma (SNUC) is a rare and aggressive skull base tumor with poor survival and limited treatment options. To date, targeted sequencing studies have identified IDH2 and SMARCB1 as potential driver alterations, but the molecular alterations found in SMARCB1 wild type tumors are unknown.

methodsWe evaluated survival outcomes in a cohort of 46 SNUC patients treated at an NCI designated cancer center and identify clinical and disease variables associated with survival on Kaplan-Meier and Cox multivariate survival analysis. We performed exome sequencing to characterize a series of SNUC tumors (n = 5) and cell line (MDA8788-6) to identify high confidence mutations, copy number alterations, microsatellite instability, and fusions. Knockdown studies using siRNA were utilized for validation of a novel PGAP3-SRPK1 gene fusion.

resultsOverall survival analysis revealed no significant difference in outcomes between patients treated with surgery +/- CRT and CRT alone. Tobacco use was the only significant predictor of survival. We also confirmed previously published findings on IDH and SMARC family mutations and identified novel recurrent aberrations in the JAK/STAT and PI3K pathways. We also validated a novel PGAP3-SRPK1 gene fusion in the SNUC cell line, and show that knockdown of the fusion is negatively associated with EGFR, E2F and MYC signaling.

conclusionCollectively, these data demonstrate recurrent alterations in the SWI/SNF family as well as IDH, JAK/STAT, and PI3K pathways and discover a novel fusion gene (PGAP3-SRPK1). These data aim to improve understanding of possible driver mutations and guide future therapeutic strategies for this disease.

Indexed as

AdultAgedAged, 80 and overCarboxylic Ester HydrolasesCarcinomaCell Line, TumorChemoradiotherapy, AdjuvantDisease-Free SurvivalFemaleFollow-Up StudiesGene Knockdown TechniquesHumansKaplan-Meier EstimateMaleMaxillary Sinus NeoplasmsMiddle AgedCarboxylic Ester HydrolasesOncogene Proteins, FusionPGAP3 protein, humanProtein Serine-Threonine KinasesReceptors, Cell SurfaceSRPK1 protein, humanSMARCASNUCSWI/SNF

Identifiers

PMID34051734
PMCPMC8164750
OpenAlexW3117869463

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.