Prospective molecular classification of endometrial carcinomas: institutional implementation, practice, and clinical experience

2021 ◽  
Author(s):  
Kelly A. Devereaux ◽  
Julianna J. Weiel ◽  
Jennifer Pors ◽  
David F. Steiner ◽  
Chandler Ho ◽  
...  
Keyword(s):  
Clinical Experience ◽  
Molecular Classification ◽  
Endometrial Carcinomas

Molecular classification of difficult to diagnose metastatic cancers and characterization of young patients: Clinical experience with the 92-gene assay in >22,000 cases.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 11554-11554
Author(s):  
F Anthony Greco ◽  
David R. Spigel ◽  
Theresa N. Operana ◽  
Brock Schroeder ◽  
Junmei Liu ◽  
...  
Keyword(s):  
Clinical Experience ◽  
Young Patients ◽  
Molecular Classification ◽  
Gene Assay

scholarly journals Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats

2009 ◽  
Vol 16 (1) ◽  
pp. 99-111 ◽  
Author(s):  
Emma Samuelson ◽  
Carola Hedberg ◽  
Staffan Nilsson ◽  
Afrouz Behboudi
Keyword(s):  
Cell Biology ◽  
Tumor Model ◽  
Molecular Classification ◽  
Female Rats ◽  
Type I ◽  
Over Expression ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Endometrial Carcinomas

Female rats of the BDII/Han inbred strain are prone to spontaneously develop endometrial carcinomas (EC) that in cell biology and pathogenesis are very similar to those of human. Human EC are classified into two major groups: Type I displays endometroid histology, is hormone-dependent, and characterized by frequent microsatellite instability and PTEN, K-RAS, and CTNNB1 (β-Catenin) mutations; Type II shows non-endometrioid histology, is hormone-unrelated, displays recurrent TP53 mutation, CDKN2A (P16) inactivation, over-expression of ERBB2 (Her2/neu), and reduced CDH1 (Cadherin 1 or E-Cadherin) expression. However, many human EC have overlapping clinical, morphologic, immunohistochemical, and molecular features of types I and II. The EC developed in BDII rats can be related to type I tumors, since they are hormone-related and histologically from endometrioid type. Here, we combined gene sequencing (Pten, Ifr1, and Ctnnb1) and real-time gene expression analysis (Pten, Cdh1, P16, Erbb2, Ctnnb1, Tp53, and Irf1) to further characterize molecular alterations in this tumor model with respect to different subtypes of EC in humans. No mutation in Pten and Ctnnb1 was detected, whereas three tumors displayed sequence aberrations of the Irf1 gene. Significant down regulation of Pten, Cdh1, p16, Erbb2, and Ctnnb1 gene products was found in the tumors. In conclusion, our data suggest that molecular features of spontaneous EC in BDII rats can be related to higher-grade human type I tumors and thus, this model represents an excellent experimental tool for research on this malignancy in human.

scholarly journals The Emerging Genomic Landscape of Endometrial Cancer

2014 ◽  
Vol 60 (1) ◽  
pp. 98-110 ◽  
Author(s):  
Matthieu Le Gallo ◽  
Daphne W Bell
Keyword(s):  
Endometrial Cancer ◽  
Copy Number ◽  
Historical Context ◽  
Molecular Classification ◽  
Genomic Alterations ◽  
Current State ◽  
Genomic Landscape ◽  
The Us ◽  
Endometrial Carcinomas

AbstractBACKGROUNDEndometrial cancer is responsible for approximately 74 000 deaths annually among women worldwide. It is a heterogeneous disease comprising multiple histologic subtypes. In the US, the majority of deaths from endometrial carcinoma are attributed to the serous and endometrioid subtypes. An understanding of the fundamental genomic alterations that drive serous and endometrioid endometrial carcinomas lays the foundation for the identification of molecular markers that could improve the clinical management of patients presenting with these tumors.CONTENTWe review the current state of knowledge regarding somatic genomic alterations that occur in serous and endometrioid endometrial tumors. We present this knowledge in a historical context by reviewing the genomic alterations that studies of individual genes and proteins have identified over the past 2 decades or so. We then review very recent comprehensive and systematic surveys of genomic, exomic, transcriptomic, epigenomic, and proteomic alterations in serous and endometrioid endometrial carcinomas.SUMMARYThe recent mapping of the genomic landscape of serous and endometrioid endometrial carcinomas has produced the first comprehensive molecular classification of these tumors, which has distinguished 4 molecular subgroups: a POLE [polymerase (DNA directed), ε, catalytic subunit] ultramutated subgroup, a hypermutated/microsatellite-unstable subgroup, a copy number–low/microsatellite-stable subgroup, and a copy number–high subgroup. This molecular classification may ultimately serve to refine the diagnosis and treatment of women with endometrioid and serous endometrial tumors.

Molecular testing in endometrial carcinoma – joint recommendation of Czech Oncological Society, Oncogynecological Section of the Czech Gynecological and Obstetrical Society, Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists

2021 ◽  
Vol 86 (4) ◽  
pp. 264-272
Author(s):  
Pavel Dundr ◽  
◽  
David Cibula ◽  
Martin Doležel ◽  
Pavel Fabián ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
European Society ◽  
Radiation Oncology ◽  
Molecular Classification ◽  
World Health ◽  
Molecular Testing ◽  
Therapeutic Implications ◽  
Health Organization ◽  
Endometrial Carcinomas

Summary: Molecular classification of endometrial carcinoma is becoming an important part of the dia gnostic process with direct therapeutic implications. Recent international guidelines, including the joint recommendation of the European Society of Gynaecological Oncology, the European Society for Radiotherapy and Oncology and the European Society of Pathology include the molecular classification into standard diagnostic algorithms. Molecular testing of endometrial carcinomas is also recommended in the latest (5th edition) of the World Health Organization classification of female genital tumors. Due to the need to implement these recommendations in practice, representatives of four professional societies of the Czech Medical Association of J. E. Purkyně (the Czech Oncological Society, the Oncogynecological Section of the Czech Gynecological and Obstetrical Society, the Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists) organized a meeting focused on this topic. Recommendation for molecular testing of endometrial carcinoma in routine dia gnostic practice in the Czech Republic.

Molecular classification of pituitary adenomas

2015 ◽  
Author(s):  
Antonio Pico ◽  
Laura Sanchez-Tejada ◽  
Ruth Sanchez-Ortiga ◽  
Rosa Camara ◽  
Cristina Lamas ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Molecular Classification

scholarly journals Normal tissue content impact on the GBM molecular classification

2020 ◽  
Author(s):  
Rodrigo Madurga ◽  
Noemí García-Romero ◽  
Beatriz Jiménez ◽  
Ana Collazo ◽  
Francisco Pérez-Rodríguez ◽  
...  
Keyword(s):  
Normal Tissue ◽  
In Silico Analysis ◽  
Molecular Classification ◽  
Gene Signature ◽  
Normal Brain ◽  
Normal Cells ◽  
Final Model ◽  
Tumor Subtypes ◽  
Tissue Content

Abstract Molecular classification of glioblastoma has enabled a deeper understanding of the disease. The four-subtype model (including Proneural, Classical, Mesenchymal and Neural) has been replaced by a model that discards the Neural subtype, found to be associated with samples with a high content of normal tissue. These samples can be misclassified preventing biological and clinical insights into the different tumor subtypes from coming to light. In this work, we present a model that tackles both the molecular classification of samples and discrimination of those with a high content of normal cells. We performed a transcriptomic in silico analysis on glioblastoma (GBM) samples (n = 810) and tested different criteria to optimize the number of genes needed for molecular classification. We used gene expression of normal brain samples (n = 555) to design an additional gene signature to detect samples with a high normal tissue content. Microdissection samples of different structures within GBM (n = 122) have been used to validate the final model. Finally, the model was tested in a cohort of 43 patients and confirmed by histology. Based on the expression of 20 genes, our model is able to discriminate samples with a high content of normal tissue and to classify the remaining ones. We have shown that taking into consideration normal cells can prevent errors in the classification and the subsequent misinterpretation of the results. Moreover, considering only samples with a low content of normal cells, we found an association between the complexity of the samples and survival for the three molecular subtypes.

scholarly journals Molecular Classification and Tumor Microenvironment Characterization of Gallbladder Cancer by Comprehensive Genomic and Transcriptomic Analysis

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 733
Author(s):  
Nobutaka Ebata ◽  
Masashi Fujita ◽  
Shota Sasagawa ◽  
Kazuhiro Maejima ◽  
Yuki Okawa ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Gallbladder Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Molecular Classification ◽  
Mesenchymal Transition ◽  
Elevated Expression ◽  
Fresh Frozen ◽  
Therapeutic Decision Making

Gallbladder cancer (GBC), a rare but lethal disease, is often diagnosed at advanced stages. So far, molecular characterization of GBC is insufficient, and a comprehensive molecular portrait is warranted to uncover new targets and classify GBC. We performed a transcriptome analysis of both coding and non-coding RNAs from 36 GBC fresh-frozen samples. The results were integrated with those of comprehensive mutation profiling based on whole-genome or exome sequencing. The clustering analysis of RNA-seq data facilitated the classification of GBCs into two subclasses, characterized by high or low expression levels of TME (tumor microenvironment) genes. A correlation was observed between gene expression and pathological immunostaining. TME-rich tumors showed significantly poor prognosis and higher recurrence rate than TME-poor tumors. TME-rich tumors showed overexpression of genes involved in epithelial-to-mesenchymal transition (EMT) and inflammation or immune suppression, which was validated by immunostaining. One non-coding RNA, miR125B1, exhibited elevated expression in stroma-rich tumors, and miR125B1 knockout in GBC cell lines decreased its invasion ability and altered the EMT pathway. Mutation profiles revealed TP53 (47%) as the most commonly mutated gene, followed by ELF3 (13%) and ARID1A (11%). Mutations of ARID1A, ERBB3, and the genes related to the TGF-β signaling pathway were enriched in TME-rich tumors. This comprehensive analysis demonstrated that TME, EMT, and TGF-β pathway alterations are the main drivers of GBC and provides a new classification of GBCs that may be useful for therapeutic decision-making.

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