These oncotarget results may reflect the unselected patient population enrolled in these studies, including lack of selection for WHO histological subtypes or molecular aberrations.

Oncotarget published “Genomic clustering analysis identification molecular subtypes of thymic epithelial tumors independent of the histological type of the World Health Organization”, which reported that genomic information from 102 evaluable TETs from the Cancer Genome Atlas dataset and from the IU-TAB-1 cell line of a clustering analysis were subjected to identify molecular subtypes of TETs.

Six new molecular subtypes of TETs from the TCGA were identified and there was no association with the WHO histological subtype.

The IU-TAB-1 cell line grouped into the TH4 molecular subtype and in vitro tests of therapeutic candidates were performed.

The susceptibility to nelfinavir was due to the gain-of-function mutation of the IU-TAB-1 cell line in PIK3CA and the amplification of genes observed in array comparative genomic hybridization including AURKA, ERBB2, KIT, PDGFRA and PDGFB, which are known to upregulate AKT while resistance to everolimus was primarily driven by upregulation of downstream signaling by KIT, PDGFRA and PDGFB in the presence of mTORC1 inhibition.

The authors of Oncotarget present a new molecular classification of TETs independent of the histological subtype of the WHO, which can be used for preclinical validation studies of potential therapeutics of interest for this rare disease.

Dr. Sukhmani K. Padda of Stanford University School of Medicine / Stanford Cancer Institute said, “Thymic epithelial tumors (TETs) are rare tumors that represent a broad spectrum of diseases from indolent thymoma to more aggressive thymic cancer.”

Thymoma subtypes include A, AB, B1, B2, B3, and other rare categories; there are also TET subtypes of thymic carcinoma and neuroendocrine thymic tumor.

Several molecular analyzes have been performed on TETs, with the Cancer Genome Atlas reporting a comprehensive multi-omic analysis of 117 TETs.

Despite the advances in molecular diagnostics, the molecular aberrations and molecular subtypes discovered by the TCGA still have no influence on therapeutic decisions.

These oncotarget results may reflect the unselected patient population enrolled in these studies, including lack of selection for WHO histological subtypes or molecular aberrations.

The goals were to identify new molecular subtypes of TETs and to investigate their association with WHO histological subtypes and to present a conceptual approach to preclinical validation of therapeutics in a molecularly classified cell line for potential further clinical investigations in this rare disease.

The Padda research team concluded in their oncotarget research result that preclinical models for TETs are limited to a handful of cell lines and clinical studies are limited to single-arm phase II studies.

This computer-aided analysis includes data from tests that are routinely used in the clinical setting, such as: B. Next generation targeted sequencing assays including gene mutations, copy number variations, and chromosomal aberrations.

In this study, computer analysis of the TCGA dataset reveals an updated molecular classification of TETs and identifies 6 unique molecular subtypes; It is important that these subtypes are independent of the WHO histological subtypes.

Only the IU-TAB-1 cell line underwent clustering analysis and was used for preclinical testing of therapeutic candidates for one of the six identified molecular subtypes from the TCGA. Although the IU-TAB-1 cell line reflects the predominant histotype of the 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 of the tumor and the presentation of a histotype, which indicates a better prognosis and a lower potential for metastasis.

Future work should therefore include further genomic characterizations and clustering analyzes of TETs, especially of metastatic tumors, as well as the generation of diverse TET cell lines in order to evaluate whether this proof of concept approach of preclinical therapeutic candidate tests in molecularly classified cell lines is promising for clinical translation Patients with this rare disease.


DOI – https: //doi.Organization/10.18632 /onkoziel.27978

Full text – https: // /Items/27978 /Text/

CorrespondenceРSukhmani K. Padda Р[email protected]

keywords – Thymic epithelial tumor, thymoma, genomics, clustering, computer analysis

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