scholarly journals Mismatch repair deficiency: a step forward personalized medicine in endometrial cancer?

2016 ◽  
Vol 4 (2) ◽  
pp. 34-41
Author(s):  
Chiara Della Pepa ◽  
Susana Banerjee ◽  
Angela George
Keyword(s):  
Endometrial Cancer ◽  
Copy Number ◽  
Current Knowledge ◽  
Prognostic Significance ◽  
Good Prognosis ◽  
The Cancer Genome Atlas ◽  
Therapeutic Implications ◽  
Repair Deficiency ◽  
Cancer Genome Atlas

Endometrial cancer (EC) is the most common female malignancy in the world, it has traditionally been classified into two subgroups based on histopathological features, however this dualistic classification does not take into consideration subtypes such as high-grade endometrioid EC. Recently, work performed as part of The Cancer Genome Atlas study has focused on molecular genomic classification of EC, with four distinct molecular subtypes described: 1. POLE ultramutated, associated with a good prognosis; 2. Microsatellite instability (MSI) hypermutated; 3. Copy number low and microsatellite stable; 4. Copy number high, serous like, associated with a poor prognosis. The subgroup of patients with MSI is of particular interest for a number of reasons, including the use of tumour screening to identify patients with Lynch syndrome, the prognostic significance of MSI, and the potential therapeutic implications. This review will focus on the current knowledge in these areas and potential future directions.

scholarly journals A Timely Update of Immunohistochemistry and Molecular Classification in the Diagnosis and Risk Assessment of Endometrial Carcinomas

2021 ◽  
Vol 145 (11) ◽  
pp. 1367-1378
Author(s):  
Minhua Wang ◽  
Pei Hui
Keyword(s):  
Copy Number ◽  
Treatment Strategies ◽  
The United States ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Molecular Profile ◽  
Cancer Genome Atlas ◽  
Endometrial Carcinomas ◽  
Genome Atlas

Context.— Endometrial carcinoma is the most common gynecologic malignancy in the United States and has been traditionally classified based on histology. However, the distinction of certain histologic subtypes based on morphology is not uncommonly problematic, and as such, immunohistochemical study is often needed. Advances in comprehensive tumor sequencing have provided novel molecular profiles of endometrial carcinomas. Four distinct molecular subtypes with different prognostic values have been proposed by The Cancer Genome Atlas program: polymerase epsilon ultramutated, microsatellite instability hypermutated, copy number low (microsatellite stable or no specific molecular profile), and copy number high (serouslike, p53 mutant). Objective.— To discuss the utilities of commonly used immunohistochemical markers for the classification of endometrial carcinomas and to review the recent advancements of The Cancer Genome Atlas molecular reclassification and their potential impact on treatment strategies. Data Sources.— Literature review and authors' personal practice experience. Conclusions.— The current practice of classifying endometrial cancers is predominantly based on morphology. The use of ancillary testing, including immunohistochemistry, is helpful in the identification, differential diagnosis, and classification of these cancers. New developments such as molecular subtyping have provided insightful prognostic values for endometrial carcinomas. The proposed The Cancer Genome Atlas classification is poised to gain further prominence in guiding the prognostic evaluation for tailored treatment strategies in the near future.

scholarly journals High miR-93 Expression Predicts Good Prognosis in Acute Myeloid Leukemia

2021 ◽  
Author(s):  
Yan Liu ◽  
Longzhen Cui ◽  
Lin Fu
Keyword(s):  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Good Prognosis ◽  
The Cancer Genome Atlas ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Prognostic Effect ◽  
Cancer Genome Atlas ◽  
Gastric Cancer Patients

Abstract Background: Overexpression of microRNA-93 (miR-93) predicted worse outcome in non-small cell lung cancer (NSCLC) and gastric cancer patients, yet the prognostic role of miR-93 in AML is still unclear.Methods: To further verify the prognostic significance of miR-93, the Cancer Genome Atlas database (TCGA) was screened and 161 AML patients with miR-93 expression information were included in our study.Results: Compared with the patients who received chemotherapy alone with lower miR-93 expression, those with higher miR-93 expression had significantly longer event-free survival (EFS) and overall survival (OS) (all P < 0.05). Moreover, the expression levels of miR-93 was no association with either EFS or OS in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Multivariate analysis confirmed that high miR-93 expression was an independent favorable factor for EFS and OS in AML patients only receiving chemotherapy (all P < 0.05).Conclusion: our study proved that high miR-93 expression could predict favorable prognosis in AML, but its prognostic effect could be overcome by allo-HSCT.

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 High miR-93 Expression Predicts Good Prognosis in Acute Myeloid Leukemia

2020 ◽  
Author(s):  
Yan Liu ◽  
Zhiheng Cheng ◽  
Longzhen Cui ◽  
Yifan Pang ◽  
Yifeng Dai ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Good Prognosis ◽  
The Cancer Genome Atlas ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Prognostic Effect ◽  
Cancer Genome Atlas ◽  
Gastric Cancer Patients

Abstract Background: Overexpression of microRNA-93 (miR-93) predicted worse outcome in non-small cell lung cancer (NSCLC) and gastric cancer patients, yet the prognostic role of miR-93 in AML is still unclear.Methods: To further verify the prognostic significance of miR-93, the Cancer Genome Atlas database (TCGA) was screened and 161 AML patients with miR-93 expression information were included in our study.Results: Compared with the patients who received chemotherapy alone with lower miR-93 expression, those with higher miR-93 expression had significantly longer event-free survival (EFS) and overall survival (OS) (all P < 0.05). Moreover, the expression levels of miR-93 was no association with either EFS or OS in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Multivariate analysis confirmed that high miR-93 expression was an independent favorable factor for EFS and OS in AML patients only receiving chemotherapy (all P < 0.05).Conclusion: our study proved that high miR-93 expression could predict favorable prognosis in AML, but its prognostic effect could be overcome by allo-HSCT.

scholarly journals Integrated mutational landscape analysis of uterine leiomyosarcomas

2021 ◽  
Vol 118 (15) ◽  
pp. e2025182118
Author(s):  
Jungmin Choi ◽  
Aranzazu Manzano ◽  
Weilai Dong ◽  
Stefania Bellone ◽  
Elena Bonazzoli ◽  
...  
Keyword(s):  
Copy Number ◽  
Muscle Layer ◽  
The Cancer Genome Atlas ◽  
Repair Deficiency ◽  
Whole Exome ◽  
Genetic Landscape ◽  
Dna Repair Deficiency ◽  
Number Variation ◽  
Fresh Frozen ◽  
Cancer Genome Atlas

Uterine leiomyosarcomas (uLMS) are aggressive tumors arising from the smooth muscle layer of the uterus. We analyzed 83 uLMS sample genetics, including 56 from Yale and 27 from The Cancer Genome Atlas (TCGA). Among them, a total of 55 Yale samples including two patient-derived xenografts (PDXs) and 27 TCGA samples have whole-exome sequencing (WES) data; 10 Yale and 27 TCGA samples have RNA-sequencing (RNA-Seq) data; and 11 Yale and 10 TCGA samples have whole-genome sequencing (WGS) data. We found recurrent somatic mutations in TP53, MED12, and PTEN genes. Top somatic mutated genes included TP53, ATRX, PTEN, and MEN1 genes. Somatic copy number variation (CNV) analysis identified 8 copy-number gains, including 5p15.33 (TERT), 8q24.21 (C-MYC), and 17p11.2 (MYOCD, MAP2K4) amplifications and 29 copy-number losses. Fusions involving tumor suppressors or oncogenes were deetected, with most fusions disrupting RB1, TP53, and ATRX/DAXX, and one fusion (ACTG2-ALK) being potentially targetable. WGS results demonstrated that 76% (16 of 21) of the samples harbored chromoplexy and/or chromothripsis. Clinically actionable mutational signatures of homologous-recombination DNA-repair deficiency (HRD) and microsatellite instability (MSI) were identified in 25% (12 of 48) and 2% (1 of 48) of fresh frozen uLMS, respectively. Finally, we found olaparib (PARPi; P = 0.002), GS-626510 (C-MYC/BETi; P < 0.000001 and P = 0.0005), and copanlisib (PIK3CAi; P = 0.0001) monotherapy to significantly inhibit uLMS-PDXs harboring derangements in C-MYC and PTEN/PIK3CA/AKT genes (LEY11) and/or HRD signatures (LEY16) compared to vehicle-treated mice. These findings define the genetic landscape of uLMS and suggest that a subset of uLMS may benefit from existing PARP-, PIK3CA-, and C-MYC/BET-targeted drugs.

scholarly journals The Prognostic Significance of MAFK and its Methylation in Cervical Cancer

2021 ◽  
Author(s):  
Mengjun Zhang ◽  
Hao Li ◽  
Yuan Liu ◽  
Siyu Hou ◽  
Ping Cui ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Aberrant Methylation ◽  
Cancer Data ◽  
Drug Candidates ◽  
Cancer Genome Atlas ◽  
Cancer Tissues

Abstract Background: The purpose of this study was to determine the value of MAFK as a biomarker of cervical cancer prognosis and to explore its methylation and possible cellular signaling pathways. Methods: We analyzed the cervical cancer data of The Cancer Genome Atlas (TCGA) through bioinformatics, including MAFK expression, methylation, prognosis and genome enrichment analysis. Results: MAFK expression was higher in cervical cancer tissues and was negatively correlated with the methylation levels of five CpG sites. MAFK is an independent prognostic factor of cervical cancer and is involved in the Nod-like receptor signaling pathway. CMap analysis screened four drug candidates for cervical cancer treatment. Conclusions: We confirmed that MAFK is a novel prognostic biomarker for cervical cancer and aberrant methylation may also affect MAFK expression and carcinogenesis. This study provides a new molecular target for the prognostic evaluation and treatment of cervical cancer.

scholarly journals Racial differences in endometrial cancer molecular portraits in The Cancer Genome Atlas

Oncotarget ◽  
2018 ◽  
Vol 9 (24) ◽  
pp. 17093-17103 ◽  
Author(s):  
David S. Guttery ◽  
Kevin Blighe ◽  
Konstantinos Polymeros ◽  
R. Paul Symonds ◽  
Salvador Macip ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Racial Differences ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

scholarly journals Study of the Female Sex Survival Advantage in Melanoma—A Focus on X-Linked Epigenetic Regulators and Immune Responses in Two Cohorts

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2082
Author(s):  
Abdullah Al Emran ◽  
Jérémie Nsengimana ◽  
Gaya Punnia-Moorthy ◽  
Ulf Schmitz ◽  
Stuart J. Gallagher ◽  
...  
Keyword(s):  
Immune Responses ◽  
Interaction Analysis ◽  
Prognostic Significance ◽  
Primary Melanoma ◽  
The Cancer Genome Atlas ◽  
Oncogenic Pathways ◽  
Cancer Genome Atlas ◽  
Epigenetic Regulators ◽  
New Treatment ◽  
Lymphoid Infiltration

Background: Survival from melanoma is strongly related to patient sex, with females having a survival rate almost twice that of males. Many explanations have been proposed but have not withstood critical scrutiny. Prior analysis of different cancers with a sex bias has identified six X-linked genes that escape X chromosome inactivation in females and are, therefore, potentially involved in sex differences in survival. Four of the genes are well-known epigenetic regulators that are known to influence the expression of hundreds of other genes and signaling pathways in cancer. Methods: Survival and interaction analysis were performed on the skin cutaneous melanoma (SKCM) cohort in The Cancer Genome Atlas (TCGA), comparing high vs. low expression of KDM6A, ATRX, KDM5C, and DDX3X. The Leeds melanoma cohort (LMC) on 678 patients with primary melanoma was used as a validation cohort. Results: Analysis of TCGA data revealed that two of these genes—KDM6A and ATRX—were associated with improved survival from melanoma. Tumoral KDM6A was expressed at higher levels in females and was associated with inferred lymphoid infiltration into melanoma. Gene set analysis of high KDM6A showed strong associations with immune responses and downregulation of genes associated with Myc and other oncogenic pathways. The LMC analysis confirmed the prognostic significance of KDM6A and its interaction with EZH2 but also revealed the expression of KDM5C and DDX3X to be prognostically significant. The analysis also confirmed a partial correlation of KDM6A with immune tumor infiltrates. Conclusion: When considered together, the results from these two series are consistent with the involvement of X-linked epigenetic regulators in the improved survival of females from melanoma. The identification of gene signatures associated with their expression presents insights into the development of new treatment initiatives but provides a basis for exploration in future studies.

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