scholarly journals Diverse ‘just-right’ levels of chromosomal instability and their clinical implications in neoadjuvant treated gastric cancer

2021 ◽  
Author(s):  
Meike Kohlruss ◽  
Marie Krenauer ◽  
Bianca Grosser ◽  
Nicole Pfarr ◽  
Moritz Jesinghaus ◽  
...  
Keyword(s):  
Chromosomal Instability ◽  
Multivariable Analysis ◽  
The Cancer Genome Atlas ◽  
Tumour Regression ◽  
Clinical Implications ◽  
Negative Prognostic Factor ◽  
Cancer Genome Atlas ◽  
Predictive And Prognostic Value ◽  
Generation Sequencing ◽  
Mutation Profiling

Abstract Background The Cancer Genome Atlas (TCGA) consortium described EBV positivity(+), high microsatellite instability (MSI-H), genomic stability (GS) and chromosomal instability (CIN) as molecular subtypes in gastric carcinomas (GC). We investigated the predictive and prognostic value of these subtypes with emphasis on CIN in the context of neoadjuvant chemotherapy (CTx) in GC. Methods TCGA subgroups were determined for 612 resected adenocarcinomas of the stomach and gastro-oesophageal junction (291 without, 321 with CTx) and 143 biopsies before CTx. EBV and MSI-H were analysed by standard assays. CIN was detected by multiplex PCRs analysing 22 microsatellite markers. Besides the TCGA classification, CIN was divided into four CIN-subgroups: low, moderate, substantial, high. Mutation profiling was performed for 52 tumours by next-generation sequencing. Results EBV(+) (HR, 0.48; 95% CI, 0.23–1.02), MSI-H (HR, 0.56; 95% CI, 0.35–0.89) and GS (HR, 0.72; 95% CI, 0.45–1.13) were associated with increased survival compared to CIN in the resected tumours. Considering the extended CIN-classification, CIN-substantial was a negative prognostic factor in uni- and multivariable analysis in resected tumours with CTx (each p < 0.05). In biopsies before CTx, CIN-high predicted tumour regression (p = 0.026), but was not prognostically relevant. Conclusion A refined CIN classification reveals tumours with different biological characteristics and potential clinical implications.

scholarly journals On the Reproducibility of TCGA Ovarian Cancer MicroRNA Profiles

2013 ◽  
Author(s):  
Ying-Wooi Wan ◽  
Claire Mach ◽  
Genevera I. Allen ◽  
Matthew Anderson ◽  
Zhandong Liu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Survival ◽  
Human Cancer ◽  
The Cancer Genome Atlas ◽  
Detection Algorithms ◽  
Level 3 ◽  
Cancer Genome Atlas ◽  
Ovarian Cancer Survival ◽  
Generation Sequencing

Dysregulated microRNA (miRNA) expression is a well-established feature of human cancer. However, the role of specific miRNAs in determining cancer outcomes remains unclear. Using Level 3 expression data from the Cancer Genome Atlas (TCGA), we identified 61 miRNAs that are associated with overall survival in 469 ovarian cancers profiled by microarray (p<0.01). We also identified 12 miRNAs that are associated with survival when miRNAs were profiled in the same specimens using Next Generation Sequencing (miRNA-Seq) (p<0.01). Surprisingly, only 1 miRNA transcript is associated with ovarian cancer survival in both datasets. Our analyses indicate that this discrepancy is due to the fact that miRNA levels reported by the two platforms correlate poorly, even after correcting for potential issues inherent to signal detection algorithms. Further investigation is warranted.

scholarly journals Molecular and phenotypic profiling of colorectal cancer patients in West Africa reveals biological insights

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Olusegun Isaac Alatise ◽  
Gregory C. Knapp ◽  
Avinash Sharma ◽  
Walid K. Chatila ◽  
Olukayode A. Arowolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
West Africa ◽  
The Cancer Genome Atlas ◽  
Cancer Center ◽  
Rectal Disease ◽  
Ras Pathway ◽  
Phenotypic Profile ◽  
Cancer Genome Atlas ◽  
Colorectal Cancer Patients ◽  
Generation Sequencing

AbstractUnderstanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is vital to addressing the regions rising burden of disease. Tissue from unselected Nigerian patients was analyzed with a multigene, next-generation sequencing assay. The rate of microsatellite instability is significantly higher among Nigerian CRC patients (28.1%) than patients from The Cancer Genome Atlas (TCGA, 14.2%) and Memorial Sloan Kettering Cancer Center (MSKCC, 8.5%, P < 0.001). In microsatellite-stable cases, tumors from Nigerian patients are less likely to have APC mutations (39.1% vs. 76.0% MSKCC P < 0.001) and WNT pathway alterations (47.8% vs. 81.9% MSKCC, P < 0.001); whereas RAS pathway alteration is more prevalent (76.1% vs. 59.6%, P = 0.03). Nigerian CRC patients are also younger and more likely to present with rectal disease (50.8% vs. 33.7% MSKCC, P < 0.001). The findings suggest a unique biology of CRC in Nigeria, which emphasizes the need for regional data to guide diagnostic and treatment approaches for patients in West Africa.

scholarly journals MSI and EBV Positive Gastric Cancer’s Subgroups and Their Link with Novel Immunotherapy

2020 ◽  
Vol 9 (5) ◽  
pp. 1427 ◽  
Author(s):  
Maria Grazia Rodriquenz ◽  
Giandomenico Roviello ◽  
Alberto D’Angelo ◽  
Daniele Lavacchi ◽  
Franco Roviello ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Chromosomal Instability ◽  
Epstein Barr Virus ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Gastric Cancers ◽  
Barr Virus ◽  
Cancer Genome Atlas ◽  
Epstein Barr ◽  
Genome Atlas

Gastric cancers have been historically classified based on histomorphologic features. The Cancer Genome Atlas network reported the comprehensive identification of genetic alterations associated with gastric cancer, identifying four distinct subtypes— Epstein-Barr virus (EBV)-positive, microsatellite-unstable/instability (MSI), genomically stable and chromosomal instability. In particular, EBV-positive and MSI gastric cancers seem responsive to novel immunotherapies drugs. The aim of this review is to describe MSI and EBV positive gastric cancer’s subgroups and their relationship with novel immunotherapy.

scholarly journals Activation of oxidative phosphorylation in TP53-inactive endometrial carcinomas with a poor prognosis

2021 ◽  
pp. ijgc-2021-002983
Author(s):  
Nobutaka Takahashi ◽  
Keiichi Hatakeyama ◽  
Takeshi Nagashima ◽  
Keiichi Ohshima ◽  
Kenichi Urakami ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Drug Targets ◽  
Poor Prognosis ◽  
Molecular Profiling ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Polymerase Epsilon ◽  
Endometrial Carcinomas ◽  
Potential Drug Targets ◽  
Generation Sequencing

ObjectiveWe aimed to identify pathways for potential therapeutic targets by conducting molecular profiling of endometrial carcinomas in patients with poor prognosis.MethodsThe classification of endometrial carcinomas has undergone a paradigm shift with the advent of next generation sequencing based molecular profiling. Although this emerging classification reflects poor prognosis in patients with endometrial carcinoma, knowledge of affected biological pathways is still lacking. In this study, 85 patients with endometrial carcinomas at the Shizuoka Cancer Center were evaluated from January 2014 to March 2019 and classified based on The Cancer Genome Atlas subgroups. The accumulation of germline and somatic mutations was determined using next generation sequencing. Gene expression profiling was used to determine the effect of TP53 inactivation on the recurrence of endometrial carcinoma. Additionally, the biological pathways associated with TP53 inactivation were estimated by pathway analysis based on gene expression.ResultsBased on The Cancer Genome Atlas classification, the ratio of polymerase-epsilon to copy number-high subgroups and the frequency of PTEN and TP53 mutations differed in patients, and mutations of ARHGAP35 observed in normal endometrium were accumulated in the polymerase-epsilon and microsatellite instability subgroups. We revealed that copy number-high reflects TP53 inactivation in endometrial carcinomas, and that TP53-inactive tumors with or without TP53 mutations have poor prognosis. Furthermore, overexpression of aurora kinase A and activation of oxidative phosphorylation were found in TP53-inactivated endometrial carcinomas, suggesting that the PI3K/mTOR and autophagy pathways are potential drug targets.DiscussionOur analysis revealed a relationship between pathways involved in oxidative phosphorylation and poor prognosis and provides insight into potential drug targets.

scholarly journals Comprehensive Immunohistochemical Study of the SWI/SNF Complex Expression Status in Gastric Cancer Reveals an Adverse Prognosis of SWI/SNF Deficiency in Genomically Stable Gastric Carcinomas

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3894
Author(s):  
Marie-Isabelle Glückstein ◽  
Sebastian Dintner ◽  
Tim Tobias Arndt ◽  
Dmytro Vlasenko ◽  
Gerhard Schenkirsch ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Therapy Resistance ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Aberrant Expression ◽  
Routine Diagnostics ◽  
Negative Prognostic Factor ◽  
Genes Encoding ◽  
Cancer Genome Atlas

The SWI/SNF complex has important functions in the mobilization of nucleosomes and consequently influences gene expression. Numerous studies have demonstrated that mutations or deficiency of one or more subunits can have an oncogenic effect and influence the development, progression, and eventual therapy resistance of tumor diseases. Genes encoding subunits of the SWI/SNF complex are mutated in approximately 20% of all human tumors. This study aimed to investigate the frequency, association with clinicopathological characteristics, and prognosis of immunohistochemical expression of proteins of the SWI/SNF complexes, SMARCA2, SMARCA4 SMARCB1, ARID1A, ARID1B, and PBRM1 in 477 adenocarcinomas of the stomach and gastroesophageal junction. Additionally, the tumors were classified immunohistochemically in analogy to The Cancer Genome Atlas (TCGA) classification. Overall, 32% of cases demonstrated aberrant expression of the SWI/SNF complex. Complete loss of SMARCA4 was detected in three cases (0.6%) and was associated with adverse clinical characteristics. SWI/SNF aberration emerged as an independent negative prognostic factor for overall survival in genomically stable patients in analogy to TCGA. In conclusion, determination of SWI/SNF status could be suggested in routine diagnostics in genomically stable tumors to identify patients who might benefit from new therapeutic options.

scholarly journals Validation and calibration of next-generation sequencing to identify Epstein-Barr virus-positive gastric cancer in The Cancer Genome Atlas

2015 ◽  
Vol 19 (2) ◽  
pp. 676-681 ◽  
Author(s):  
M. Constanza Camargo ◽  
Reanne Bowlby ◽  
Andy Chu ◽  
Chandra Sekhar Pedamallu ◽  
Vesteinn Thorsson ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Next Generation Sequencing ◽  
Epstein Barr Virus ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Barr Virus ◽  
Cancer Genome Atlas ◽  
Epstein Barr ◽  
Generation Sequencing ◽  
Genome Atlas

scholarly journals A concurrent canonical and modified miRNAome pan-cancer study on TCGA and TARGET cohorts leads to an enhanced resolution in cancer

2021 ◽  
Author(s):  
Rosario Distefano ◽  
Luisa Tomasello ◽  
Gian Luca Rampioni Vinciguerra ◽  
Pierluigi Gasparini ◽  
Yujia Xiang ◽  
...  
Keyword(s):  
The Cancer Genome Atlas ◽  
Pediatric Tumor ◽  
Enhanced Resolution ◽  
Cancer Field ◽  
Cancer Genome Atlas ◽  
Simultaneous Study ◽  
And Function ◽  
Mirna Editing ◽  
Pan Cancer ◽  
Generation Sequencing

MiRNA Epitranscriptomics has placed a new layer of complexity in the cancer field. Despite miRNA editing and shifted miRNA isoforms are gaining attention due to recent improvements in next-generation sequencing, a simultaneous study of both modifications in cancer is still missing. Here, we concurrently profiled multiple miRNA modifications, such as A-to-I RNA editing and shifted miRNA isoforms, in >13K adult and pediatric tumor samples across 38 distinct cancer cohorts from The Cancer Genome Atlas and The Therapeutically Applicable Research to Generate Effective Treatments datasets. We investigated the differences among canonical miRNAs and a wider comprehensive miRNAome from the expression, clustering, dysregulation, and prognostic perspective. Interestingly, the wider miRNAome boosted clustering results, uniquely outlining cohorts' clinical-pathological features. The abundance of expressed miRNA isoforms directly related to the activation/deactivation of critical carcinogenesis pathways. We found dysregulated modified miRNAs characterized by an opposite expression trend than their canonical counterparts in cancer, potentially impacting their targetome and function. Our study emphasizes the importance of modified miRNAs as potential cancer biomarkers and gene expression regulators, outlining once more the importance of going beyond the well-established paradigm of one-mature-miRNA per miRNA arm.

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