(Press-News.org) Oncotarget published "Genomic clustering analysis identifies molecular subtypes of thymic epithelial tumors independent of World Health Organization histologic type" which reported that genomic information from 102 evaluable TETs from The Cancer Genome Atlas dataset and from the IU-TAB-1 cell line underwent clustering analysis to identify molecular subtypes of TETs.
Six novel molecular subtypes of TETs from the TCGA were identified, and there was no association with WHO histologic subtype.
The IU-TAB-1 cell line clustered into the TH4 molecular subtype and in vitro testing of candidate therapeutics was performed.
Sensitivity to nelfinavir was due to the IU-TAB-1 cell line's gain-of function mutation in PIK3CA and amplification of genes observed from array comparative genomic hybridization, including AURKA, ERBB2, KIT, PDGFRA and PDGFB, that are known upregulate AKT, while resistance to everolimus was primarily driven by upregulation of downstream signaling of KIT, PDGFRA and PDGFB in the presence of mTORC1 inhibition.
The Oncotarget authors present a novel molecular classification of TETs independent of WHO histologic subtype, which may be used for preclinical validation studies of potential candidate therapeutics of interest for this rare disease.
Dr. Sukhmani K. Padda from The Stanford University School of Medicine/Stanford Cancer Institute said, "Thymic epithelial tumors (TETs) are rare tumors that represent a wide spectrum of disease from the indolent thymoma to the more aggressive thymic carcinoma."
Thymoma subtypes include A, AB, B1, B2, B3, and other rare categories; in addition, there are TET subtypes of thymic carcinoma and thymic neuroendocrine tumor.
There have been several molecular analyses performed on TETs, with the The Cancer Genome Atlas reporting on a comprehensive multi-omic analysis of 117 TETs.
Despite the advancement in molecular diagnostics, the molecular aberrations and molecular subtypes discovered from the TCGA have not yet affected therapeutic decisions.
These Oncotarget results may reflect the unselected patient population enrolled in these studies, including no selection for WHO histologic subtype or molecular aberrations.
The goals were to identify novel molecular subtypes of TETs and examine their association with WHO histologic subtypes, and to present a proof-of-concept approach of preclinical validation of candidate therapeutics in a molecularly classified cell line for potential further clinical investigation in this rare disease.
The Padda Research Team concluded in their Oncotarget Research Output that preclinical models for TETs are limited to a handful of cell lines and clinical trials are limited to single-arm phase II studies.
This computational analysis involves data available from tests used routinely in the clinical setting such as targeted next generation sequencing assays, including gene mutations, copy number variations, and chromosomal aberrations.
In this study, computational analysis of the TCGA dataset reveals an updated molecular classification of TETs and identifies 6 unique molecular subtypes; importantly, these subtypes are independent of WHO histologic subtypes.
Only the IU-TAB-1 cell line underwent clustering analysis and was used for preclinical testing of candidate therapeutics for one of the six identified molecular subtypes from the TCGA. Although the IU-TAB-1 cell line reflects the predominant histotype of type AB thymoma from the TCGA dataset and has been extensively characterized by both whole exome sequencing and aCGH, its inherent limitations include generation from an early stage tumor and representation of a histotype that portends a better prognosis and less metastatic potential.
Therefore, future work should involve further genomic characterization and clustering analyses of TETs, particularly from metastatic tumors, and generation of diverse TET cell lines to evaluate whether this proof-of-concept approach of preclinical candidate therapeutic testing in molecularly classified cell lines is promising for clinical translation in patients with this rare disease.
INFORMATION:
DOI - https://doi.org/10.18632/oncotarget.27978
Full text - https://www.oncotarget.com/article/27978/text/
Correspondence to - Sukhmani K. Padda - sukhmani.padda@cshs.org
Keywords - thymic epithelial tumor, thymoma, genomics, clustering, computational analysis
About Oncotarget
Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.
To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:
SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/
Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls
Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957x105
Copyright © 2021 Impact Journals, LLC
Impact Journals is a registered trademark of Impact Journals, LLC
New research from Bocconi University in Milan highlights that, contrary to received wisdom, connections to organized crime harm a company's financial performance and increase by 25.5% its likelihood to go bust.
Using a novel dataset from AISI, the Italian Internal Intelligence and Security agency, Bocconi professors Antonio Marra, Donato Masciandaro, and Nicola Pecchiari in a paper co-authored with Pietro Bianchi (Florida International University) published online in The Accounting Review, identify 1,840 criminally connected firms headquartered in Italy's Lombardy region.
Lombardy, the Northern Italian region around Milan, is not ...
A relaxing vacation on the beach frees us from many of the worries of everyday life. But the sand not only cleans the head and soul of vacationers - it also cleans the seawater.
Coastal sands are so-called biocatalytic filters. Hundreds of thousands of bacteria live on each grain of sand, and they process, for example, nitrogen and carbon from the seawater that flows through the sands. In this way, the sands act like giant, purifying filters. Much of what the seawater washes into the ground does not come out again.
A study by researchers at the Max Planck Institute for Marine Microbiology in Bremen, Germany, published in the journal ISME Communications, now shows that the bacteria living on the sand are very different from the ones in seawater. And while the bacterial ...
Students who participated in a meditation-based Quiet Time program utilizing the Transcendental Meditation (TM) technique for four months had significant improvements in overall emotional stress symptoms, quality of sleep, and English Language Arts (ELA) academic achievement according to a new randomized controlled trial published last month in Education. The study was conducted by researchers from the Center for Wellness and Achievement in Education and Stanford University. This was the first randomized control trial to investigate the effects of TM on standardized academic tests.
"Students have been experiencing increased levels ...
An adhesive tape patented by Staffordshire University researchers to recover trace evidence from crimes scenes is being adopted to analyse microplastics more efficiently.
Man-made polymer particles or ‘microplastics’ are proven to be present in land, air and water environments. However, despite extensive global studies, there is no standardised approach for their collection and analysis.
Currently, studies regularly involve retrieving microplastic samples from water using a filtration method. Samples are commonly analysed in situ on the filter or after removal from it by ...
Smartphone gaming can be harmful to players who game to escape their negative mood and feelings of boredom, a new study has found.
Researchers at the University of Waterloo found that bored "escape players"--those who have difficulty engaging with the real environment and sustaining attention--may seek "flow," which is a deep and effortless state of concentration in an activity linked to loss of awareness of time and space.
"We found that people who experience intense boredom frequently in everyday life reported playing smartphone games to escape or alleviate these feelings ...
As the world warms, sweeping changes in marine nutrients seem like an expected consequence of increased ocean temperatures. However, the reality is more complicated. New research suggests that processes below the ocean surface may be controlling what is happening above.
Plankton are some of the most numerous and important organisms in the ocean. The balance of chemical elements inside them varies and is critical to shaping many marine processes, including the food web and the global carbon cycle. Temperature has been traditionally thought to control the ratio of these elements. However, a new study suggests this balance is largely dependent on activity in the subsurface ...
Curtin University research has found quit support for smoking mothers should continue even after their first babies are born, given that many of those women will become pregnant again, and that quitting can substantially reduce the risk of future preterm births.
The longitudinal study examined the records and histories across 23 years, of 63,540 Australian women with more than one child, who smoked during their first pregnancy.
Lead researcher, Professor Gavin Pereira form Curtin's School of Population Health said more than one third of women who smoked during pregnancy were able to stop smoking ...
The Xerces blue butterfly was last seen flapping its iridescent periwinkle wings in San Francisco in the early 1940s. It's generally accepted to be extinct, the first American insect species destroyed by urban development, but there are lingering questions about whether it was really a species to begin with, or just a sub-population of another common butterfly. In a new study in Biology Letters, researchers analyzed the DNA of a 93-year-old Xerces blue specimen in museum collections, and they found that its DNA is unique enough to merit being considered a species. The study confirms that yes, the Xerces blue really ...
Sophia Antipolis, 21 July 2021: A study of more than 18 million pregnancies has shown a strong and graded relationship between women's heart health and pregnancy outcomes. The research is published today in the European Journal of Preventive Cardiology, a journal of the European Society of Cardiology (ESC).1
The researchers examined the presence of four risk factors for cardiovascular disease in women prior to pregnancy: unhealthy body weight, smoking, hypertension and diabetes. The likelihood of key pregnancy complications - maternal intensive care unit (ICU) admission, preterm birth, low birthweight and foetal death - rose incrementally with the number of pre-pregnancy cardiovascular risk factors.
"Individual cardiovascular risk factors, such as obesity and hypertension, present ...
Any life identified on planets orbiting white dwarf stars almost certainly evolved after the star's death, says a new study led by the University of Warwick that reveals the consequences of the intense and furious stellar winds that will batter a planet as its star is dying. The research is published in Monthly Notices of the Royal Astronomical Society, and lead author Dr Dimitri Veras will present it today (21 July) at the online National Astronomy Meeting (NAM 2021).
The research provides new insight for astronomers searching for signs of life around these dead stars by examining the impact that their ...
