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.

scholarly journals Genome-Based Classification and Therapy of Prostate Cancer

Diagnostics ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 62 ◽  
Author(s):  
Arlou Angeles ◽  
Simone Bauer ◽  
Leonie Ratz ◽  
Sabine Klauck ◽  
Holger Sültmann
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Molecular Classification ◽  
Therapy Resistance ◽  
Clinical Practices ◽  
Molecular Alterations ◽  
The Past ◽  
Cancer Genomes ◽  
Treatment Concepts

In the past decade, multi-national and multi-center efforts were launched to sequence prostate cancer genomes, transcriptomes, and epigenomes with the aim of discovering the molecular underpinnings of tumorigenesis, cancer progression, and therapy resistance. Multiple biological markers and pathways have been discovered to be tumor drivers, and a molecular classification of prostate cancer is emerging. Here, we highlight crucial findings of these genome-sequencing projects in localized and advanced disease. We recapitulate the utility and limitations of current clinical practices to diagnosis, prognosis, and therapy, and we provide examples of insights generated by the molecular profiling of tumors. Novel treatment concepts based on these molecular alterations are currently being addressed in clinical trials and will lead to an enhanced implementation of precision medicine strategies.

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.

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

scholarly journals Pseudohypoparathyroidism: Diagnosis and Treatment

2011 ◽  
Vol 96 (10) ◽  
pp. 3020-3030 ◽  
Author(s):  
Giovanna Mantovani
Keyword(s):  
Evidence Synthesis ◽  
Diagnostic Procedures ◽  
Type I ◽  
Epigenetic Alterations ◽  
Molecular Alterations ◽  
Gnas Gene ◽  
Type Ia ◽  
Pubmed Search ◽  
Actual Classification

Abstract Context: The term pseudohypoparathyroidism (PHP) indicates a group of heterogeneous disorders whose common feature is represented by impaired signaling of various hormones (primarily PTH) that activate cAMP-dependent pathways via Gsα protein. The two main subtypes of PHP, PHP type Ia, and Ib (PHP-Ia, PHP-Ib) are caused by molecular alterations within or upstream of the imprinted GNAS gene, which encodes Gsα and other translated and untranslated products. Evidence acquisition: A PubMed search was used to identify the available studies (main query terms: pseudohypoparathyroidism; Albright hereditary osteodystrophy; GNAS; GNAS1; progressive osseous heteroplasia). The most relevant studies until February 2011 have been included in the review. Evidence synthesis and conclusions: Despite the first description of this disorder dates back to 1942, recent findings indicating complex epigenetic alterations beside classical mutations at the GNAS complex gene, pointed out the limitation of the actual classification of the disease, resulting in incorrect genetic counselling and diagnostic procedures, as well as the gap in our actual knowledge of the pathogenesis of these disorders. This review will focus on PHP type I, in particular its diagnosis, classification, treatment, and underlying molecular alterations.

Molecular Genetics of Endometrial Carcinoma

2019 ◽  
Vol 14 (1) ◽  
pp. 339-367 ◽  
Author(s):  
Daphne W. Bell ◽  
Lora Hedrick Ellenson
Keyword(s):  
Endometrial Carcinoma ◽  
Copy Number ◽  
Clear Cell ◽  
Genomic Analysis ◽  
Molecular Classification ◽  
The United States ◽  
The Cancer Genome Atlas ◽  
Therapeutic Implications ◽  
Molecular Features ◽  
Endometrial Carcinomas

Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. Endometrioid endometrial carcinomas constitute approximately 85% of newly diagnosed cases; serous carcinomas represent approximately 3–10% of diagnoses; clear cell carcinoma accounts for <5% of diagnoses; and uterine carcinosarcomas are rare, biphasic tumors. Longstanding molecular observations implicate PTEN inactivation as a major driver of endometrioid carcinomas; TP53 inactivation as a major driver of most serous carcinomas, some high-grade endometrioid carcinomas, and many uterine carcinosarcomas; and inactivation of either gene as drivers of some clear cell carcinomas. In the past decade, targeted gene and exome sequencing have uncovered additional pathogenic aberrations in each histotype. Moreover, an integrated genomic analysis by The Cancer Genome Atlas (TCGA) resulted in the molecular classification of endometrioid and serous carcinomas into four distinct subgroups, POLE (ultramutated), microsatellite instability (hypermutated), copy number low (endometrioid), and copy number high (serous-like). In this review, we provide an overview of the major molecular features of the aforementioned histopathological subtypes and TCGA subgroups and discuss potential prognostic and therapeutic implications for endometrial carcinoma.

scholarly journals DNA methylation profiling for molecular classification of adult diffuse lower-grade gliomas

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sandra Ferreyra Vega ◽  
Thomas Olsson Bontell ◽  
Alba Corell ◽  
Anja Smits ◽  
Asgeir Store Jakola ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Classification ◽  
Lower Grade ◽  
Who Grade ◽  
Class Prediction ◽  
Mutation Status ◽  
Molecular Features ◽  
Dna Methylation Profiling ◽  
Methylation Profiling

Abstract Background DNA methylation profiling has facilitated and improved the classification of a wide variety of tumors of the central nervous system. In this study, we investigated the potential utility of DNA methylation profiling to achieve molecular diagnosis in adult primary diffuse lower-grade glioma (dLGG) according to WHO 2016 classification system. We also evaluated whether methylation profiling could provide improved molecular characterization and identify prognostic differences beyond the classical histological WHO grade together with IDH mutation status and 1p/19q codeletion status. All patients diagnosed with dLGG in the period 2007–2016 from the Västra Götaland region in Sweden were assessed for inclusion in the study. Results A total of 166 dLGG cases were subjected for genome-wide DNA methylation analysis. Of these, 126 (76%) were assigned a defined diagnostic methylation class with a class prediction score ≥ 0.84 and subclass score ≥ 0.50. The assigned methylation classes were highly associated with their IDH mutation status and 1p/19q codeletion status. IDH-wildtype gliomas were further divided into subgroups with distinct molecular features. Conclusion The stratification of the patients by methylation profiling was as effective as the integrated WHO 2016 molecular reclassification at predicting the clinical outcome of the patients. Our study shows that DNA methylation profiling is a reliable and robust approach for the classification of dLGG into molecular defined subgroups, providing accurate detection of molecular markers according to WHO 2016 classification.

Molecular classification of endometrial cancers translated into practice

2021 ◽  
Vol 86 (4) ◽  
pp. 258-262
Author(s):  
Jiří Presl ◽  
◽  
Tomáš Vaněček ◽  
Michael Michal ◽  
Jiří Bouda ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Current Knowledge ◽  
Molecular Genetic ◽  
Epidemiological Data ◽  
Molecular Classification ◽  
The Cancer Genome Atlas ◽  
Treatment Regimens ◽  
Molecular Features ◽  
Practice Methods

Summary: Objective: The main objective of the article is to clearly inform healthcare professionals about the newly implemented molecular classification of endometrial cancer into practice. Methods: Summary of current knowledge, recommendations and new procedures relating to molecular genetic examination of the tissues of patients with endometrial carcinoma. Results: Endometrial cancer is currently diagnosed on the base of histopathological morphology. According to the classical Bokhman division, we distinguish between two relatively wide groups of tumors which are different in pathogenesis: type I – estrogen-dependent tumors, clinically usually indolent, and type II – non-endometroid tumors, clinically aggressive, without dependence on estrogen stimulation. This classification fulfills a  didactic purpose and provides easy orientation for epidemiological data, but is not suitable for stratification due to the overlap of clinical, pathological and molecular features. The Cancer Genome Atlas project classifies endometrial tumors into 4  groups based on molecular genetic features. Conclusion: Integration of the histopathological findings along with molecular classification appears to be the best approach for evaluating each individual tumor. This will help to achieve the ideal stratifi cation of patients for treatment regimens.

scholarly journals Integrative Analysis Identifies Multi-Omics Signatures That Drive Molecular Classification of Uveal Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6168
Author(s):  
Qianxing Mo ◽  
Lixin Wan ◽  
Michael J. Schell ◽  
Heather Jim ◽  
Shelley S. Tworoger ◽  
...  
Keyword(s):  
Risk Groups ◽  
Molecular Classification ◽  
Underlying Mechanism ◽  
Integrative Analysis ◽  
Molecular Alterations ◽  
Expression Of Genes ◽  
Immune System Cell ◽  
Number Variation ◽  
And Migration

By iCluster analysis, we found that the integrative molecular classification of the UM was primarily driven by DNA copy number variation on chromosomes 3, 6 and 8, differential methylation and expression of genes involved in the immune system, cell morphogenesis, movement and migration, and differential mutation of genes including GNA11, BAP1, EIF1AX, SF3B1 and GNAQ. Integrative analysis revealed that pathways including IL6/JAK/STAT3 signaling, angiogenesis, allograft rejection, inflammatory response and interferon gamma response were hypomethylated and up-regulated in the M3 iSubtype, which was associated with a worse overall survival, compared to the D3 iSubtype. Using two independent gene expression datasets, we demonstrated that the subtype-driving genes had an excellent prognostic power in classifying UM into high- or low-risk groups for metastasis. Integrative analysis of UM multi-omics data provided a comprehensive view of UM biology for understanding the underlying mechanism leading to UM metastasis. The concordant molecular alterations at multi-omics levels revealed by our integrative analysis could be used for patient stratification towards personalized management and surveillance.

scholarly journals Review of immunohistochemical typing of endometrial carcinoma at the Lagos University Teaching Hospital

2019 ◽  
Vol 19 (3) ◽  
pp. 2468-2475
Author(s):  
Olayemi Olubunmi Dawodu ◽  
Kehinde Sharafadeen Okunade ◽  
Adetola Daramola ◽  
Adekunbiola Aina Fehintola Banjo
Keyword(s):  
Teaching Hospital ◽  
Endometrial Adenocarcinoma ◽  
University Teaching ◽  
Type I ◽  
Type Ii ◽  
Ki 67 ◽  
Nigerian Women ◽  
Reasonable Proportion ◽  
Endometrial Carcinomas

Background: Categorization of endometrial carcinomas as type I and II provides useful insights into their different risk factors, pathogenesis and biologic behaviours.Aim: To determine the immunohistochemical classifications of endometrial carcinomas in Nigerian women.Design: A retrospective review of histopathologic slides of cases of endometrial carcinomas seen at the Lagos University Teaching Hospital (LUTH) over a 5-year period. The slides were reviewed, and the diagnoses made according to the WHO nomenclature. The classification of endometrial carcinomas into Type I and II was made by immunohistochemistry using antibodies to ER, PR, p53 and Ki-67.Results: Eight cases of endometrial adenocarcinoma were reported accounting for 53.3% of all endometrial malignancies. Of these, only 1 case showed the classic type I immunophenotype while type II staining pattern was seen in 4 cases. The remaining 3 cases had equivocal immunophenotypes: one was p53+ but showed ER+, PR+ and high Ki-67 index; the second was p53-, ER+, PR+ but had a high Ki-67 expression; while the last was p53-, but ER-, PR- and had high Ki-67 expression.Conclusion: Endometrial carcinomas in Nigerian women are more likely to be type II carcinomas. A reasonable proportion of the cases were equivocal thus requiring further categorization with molecular studies.Keywords: Endometrial carcinomas, immunohistochemistry, LUTH, Nigerian.

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