Evidence map›Paper›PMID 31745703›Full record

ArticleJournal of cancer research and clinical oncology2020

Transcriptome analysis reveals overlap in fusion genes in a phase I clinical cohort of TNBC and HGSOC patients treated with buparlisib and olaparib.

Julia Eismann, Yujing J Heng, Johannes M Waldschmidt, Ioannis S Vlachos, Kathryn P Gray, Ursula A Matulonis, Panagiotis A Konstantinopoulos, Charles J Murphy, Sheida Nabavi, Gerburg M Wulf

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cancer research and clinical oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01623349 (Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent Triple Negative Breast Cancer or High Grade Serous Ovarian Cancer), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 33% 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.

NCT01623349 phase1completednot on this map

Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent Triple Negative Breast Cancer or High Grade Serous Ovarian Cancer

TypeinterventionalSponsorDana-Farber Cancer InstituteRan2012 to 2020Enrolled118ConditionsOvarian Cancer, Breast CancerArmsBKM120 and Olaparib, BYL719 and Olaparib
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
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  4. Review
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

10 authors at 5 institutions in 2 countries.

Julia EismannDepartment of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Yujing J HengHarvard Medical School, Boston, MA, USA.
Johannes M WaldschmidtHarvard Medical School, Boston, MA, USA.
Ioannis S VlachosHarvard Medical School, Boston, MA, USA.
Kathryn P GrayHarvard Medical School, Boston, MA, USA.
Ursula A MatulonisHarvard Medical School, Boston, MA, USA.
Panagiotis A KonstantinopoulosHarvard Medical School, Boston, MA, USA.
Charles J MurphyInstitute for Computational Biomedicine, Weill Cornell Medical College, New York, NY, USA.
Sheida NabaviDepartment of Computer Science and Engineering, Institute of System Genomics, University of Connecticut, Storrs, USA.
Gerburg M WulfDepartment of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA. gwulf@bidmc.harvard.edu.ORCID http://orcid.org/0000-0001-7868-6231
Beth Israel Deaconess Medical Center · USHarvard University · USBroad Institute · USCornell University · USUniversity of Connecticut · US

Funding

Novel integrative method to detect biomakers of breast cancer resistanceR00LM011595 · NLM · UNIVERSITY OF CONNECTICUT STORRS · PI NABAVI, SHEIDA · 2015 to 2017
$597k
Novel integrative method to detect biomakers of breast cancer resistanceK99LM011595 · NLM · HARVARD MEDICAL SCHOOL · PI NABAVI, SHEIDA · 2013 to 2014
$172k
Deutsche Forschungsgemeinschaft Postdoctoral FellowshipDeutsche Krebshilfe Mildred-Scheel Postdoctoral FellowshipEntertainment Industry Foundation SU2C-AACR-DT0209NIH HHS K99LM011595NLM NIH HHS K99 LM011595NLM NIH HHS R00 LM011595
6 · The paper itself

Abstract

purposeFusion genes can be therapeutically relevant if they result in constitutive activation of oncogenes or repression of tumor suppressors. However, the prevalence and role of fusion genes in female cancers remain largely unexplored. Here, we investigate the fusion gene landscape in triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSOC), two subtypes of female cancers with high molecular similarity but limited treatment options at present.

methodsRNA-seq was utilized to identify fusion genes in a cohort of 18 TNBC and HGSOC patients treated with the PI3K inhibitor buparlisib and the PARP inhibitor olaparib in a phase I clinical trial (NCT01623349). Differential gene expression analysis was performed to assess the function of fusion genes in silico. Finally, these findings were correlated with the reported clinical outcomes.

resultsA total of 156 fusion genes was detected, whereof 44/156 (28%) events occurred in more than one patient. Low recurrence across samples indicated that the majority of fusion genes were private passenger events. The long non-coding RNA MALAT1 was involved in 97/156 (62%) fusion genes, followed in prevalence by MUC16, FOXP1, WWOX and XIST. Gene expression of FOXP1 was significantly elevated in patients with vs. without FOXP1 fusion (P= 0.02). From a clinical perspective, FOXP1 fusions were associated with a favorable overall survival.

conclusionsIn summary, this study provides the first characterization of fusion genes in a cohort of TNBC and HGSOC patients. An improved mechanistic understanding of fusion genes will support the future identification of innovative therapeutic approaches for these challenging diseases.

Indexed as

Gene FusionAdultAgedAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsClinical Trials, Phase I as TopicCystadenocarcinoma, SerousFemaleForkhead Transcription FactorsGene Expression ProfilingHumansMiddle AgedMorpholinesOvarian NeoplasmsPhthalazinesPiperazinesAminopyridinesForkhead Transcription FactorsFOXP1 protein, humanMorpholinesNVP-BKM120olaparibPhthalazinesPiperazinesRepressor ProteinsBreast cancerFusion geneGenomic profilingOvarian cancerRNA-seq

Identifiers

PMID31745703
PMCPMC6985087
OpenAlexW2991367315

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Registered trials

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.