scholarly journals TERT aberrancies: a screening tool for malignancy in follicular thyroid tumours

2018 ◽  
Vol 25 (7) ◽  
pp. 723-733 ◽  
Author(s):  
Johan O Paulsson ◽  
Ninni Mu ◽  
Ivan Shabo ◽  
Na Wang ◽  
Jan Zedenius ◽  
...  
Keyword(s):  
Screening Tool ◽  
Gene Copy Number ◽  
Promoter Hypermethylation ◽  
Malignant Potential ◽  
Gene Copy ◽  
Clinical Parameters ◽  
Uncertain Malignant Potential ◽  
Increased Risk ◽  
Promoter Mutations

Telomerase reverse transcriptase (TERT) promoter mutations have been linked to adverse clinical parameters in thyroid cancer, butTERT-expressing tumours are not always mutated. Little is known regarding otherTERT-related genetic aberrations. To delineate the role ofTERTgene aberrancies in follicular thyroid tumours, 95 follicular carcinomas (FTCs), 43 follicular adenomas (FTAs) and 33 follicular tumours of uncertain malignant potential (FT-UMPs) were collected. The tumours were assayed forTERTexpression,TERTpromoter mutations,TERTpromoter hypermethylation andTERTgene copy number (CN) alterations and the results were compared to clinical parameters. Cases with mutation, detectable mRNA expression, CN gain or hypermethylation were classified asTERTaberrant, and these aberrancies were regularly found in FTC and FT-UMP but uncommonly found in FTA. In total, 59% FTCs and 63% FT-UMPs exhibited one or more of theseTERTgene aberrancies. Moreover, 24 out of 28 FTCs (86%) withTERTexpression displayed an evidentTERTgene aberration, and statistics showed an increased risk for relapse in FTCs withTERTexpression, CN gain or hypermethylation. We conclude thatTERTexpression in follicular thyroid tumours is coupled to promoter mutations, CN gain and increased promoter methylation. The molecular similarities regardingTERTaberrations between the FTC and FT-UMP groups indicate that a significant subset of FT-UMP cases may display future recurrences.TERTaberrancies are thus promising as future additional markers for determining malignant potential of follicular thyroid tumours.

scholarly journals Comprehensive Assessment of Diet Quality and Risk of Precursors of Early-Onset Colorectal Cancer

2020 ◽  
Author(s):  
Xiaobin Zheng ◽  
Jinhee Hur ◽  
Long H Nguyen ◽  
Jie Liu ◽  
Mingyang Song ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Diet Quality ◽  
Early Onset ◽  
Strong Support ◽  
Healthy Eating Index ◽  
Malignant Potential ◽  
Poor Diet ◽  
Increased Risk

Abstract Background The role of poor diet quality in the rising incidence of colorectal cancer (CRC) diagnosed under age 50 has not been explored. Based on molecular features of early-onset CRC, early-onset adenomas are emerging surrogate endpoints. Methods In a prospective cohort study (Nurses’ Health Study II), we evaluated two empirical dietary patterns (Western and prudent) and three recommendation-based indexes (Dietary Approaches to Stop Hypertension [DASH], Alternative Mediterranean Diet [AMED], and Alternative Healthy Eating Index [AHEI]-2010) with risk of early-onset adenoma overall and by malignant potential (high-risk: ≥1 cm, tubulovillous/villous histology, high-grade dysplasia, or ≥ 3 adenomas), among 29474 women with ≥1 lower endoscopy before age 50 (1991-2011). Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results We documented 1157 early-onset adenomas with 375 of high-risk. Western diet was positively, whereas prudent diet, DASH, AMED, and AHEI-2010 were inversely associated with risk of early-onset adenoma. The associations were largely confined to high-risk adenomas (OR [95% CI] for the highest versus lowest quintile: Western = 1.67 [1.18 to 2.37]; prudent = 0.69 [0.48 to 0.98]; DASH = 0.65 [0.45 to 0.93]; AMED = 0.55 [0.38 to 0.79]; AHEI-2010 = 0.71 [0.51 to 1.01]; all P  trend≤.03), driven by those identified in the distal colon and rectum (all P  trend≤.04 except AMED: Ptrend=.14). Conclusion Poor diet quality was associated with an increased risk of early-onset distal and rectal adenomas of high malignant potential. These findings provide preliminary but strong support to the role of diet in early-onset CRC.

The Role of Cell Growth-Related Gene Copy Number Variation in Autoimmune Thyroid Disease

2019 ◽  
Vol 195 (2) ◽  
pp. 409-416 ◽  
Author(s):  
Yunfeng Guan ◽  
Lixiang Liu ◽  
Qingzhen Jia ◽  
Xing Jin ◽  
Yi Pang ◽  
...  
Keyword(s):  
Cell Growth ◽  
Copy Number ◽  
Autoimmune Thyroid Disease ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Related Gene ◽  
Autoimmune Thyroid ◽  
Gene Copy Number Variation ◽  
Number Variation

EGFR gene copy number alterations are not a useful screening tool for predicting EGFR mutation status in lung adenocarcinoma

Pathology ◽  
2014 ◽  
Vol 46 (1) ◽  
pp. 32-36
Author(s):  
Prudence A. Russell ◽  
Y.U. Yong ◽  
D.O. Hongdo ◽  
Timothy D. Clay ◽  
Melissa M. Moore ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Copy Number ◽  
Screening Tool ◽  
Egfr Mutation ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Copy Number Alterations ◽  
Mutation Status ◽  
Egfr Gene

Frequent LOH of CYP2D6 in ER+ breast cancer determined by next-generation sequencing (NGS).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 534-534
Author(s):  
Mark J. Ratain ◽  
James Sun ◽  
Yusuke Nakamura ◽  
Nancy J Cox ◽  
Tarek Sahmoud ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sequence Data ◽  
Biological Significance ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Full Cohort ◽  
Next Generation Sequencing Ngs ◽  
Apparent Association

534 Background: The role of CYP2D6 genetic variation in predicting response to tamoxifen in ER+ breast cancer is a subject of ongoing debate. There has been great variability in approaches to both genotyping and phenotyping, and in particular many investigators have extracted DNA from breast cancer samples rather than peripheral blood. We hypothesized that CYP2D6 gene copy number alterations are common in ER+ breast cancer, affecting genotype results, and used NGS to characterize CYP2D6 in patients with ER+ disease. Methods: CYP2D6 sequencing was performed as part of a comprehensive NGS profile of cancer-related genes for 261 predominantly relapsed and metastatic ER+ breast cancer FFPE specimens. Sequence data were resolved into genotypes according to the * allele nomenclature. Tumor LOH was determined at CYP2D6, and its error impact on genotyping methods was estimated. To assess biological significance, the prevalence of CYP2D6 alleles and LOH in ER+ disease was compared against a control set of 99 ER- tumors. Results: CYP2D6 allele frequencies in our full cohort (ER+, 261; ER-, 99) were consistent with prior studies; 64.4%, 16.8%, 9.0% vs. 63.1%, 17.2%, 7.0% for *1/*2, *4, and *41 respectively, and 1%-2% for the rarer alleles *9, *10, and *5. The rate of CYP2D6 LOH was higher in ER+ disease (41% vs. 26%, p<0.01), with all excess arising from copy-loss (as opposed to copy-neutral) changes (22% vs. 7%, p<0.002). The estimated impact of LOH on germline genotype assessment from tumor was considerable; an assay sensitive at >20% minor allele frequency (e.g., Sanger sequencing) can misclassify >10% of heterozygotes, leading to significant Hardy-Weinberg disequilibrium (e.g., p=8.3x10-8 for *4). Interestingly, an enrichment of reduced or non-functional CYP2D6 alleles in ER+ samples was observed (61% vs. 47%, p<0.03). Conclusions: Our results demonstrate the distorting effect of extensive LOH on genotype assessment of CYP2D6 in breast cancer. Therefore, tumor DNA should not be routinely used for determination of germline 2D6 genotype, although it appears possible to use NGS. The apparent association between reduced function CYP2D6 alleles and ER+ breast cancer in our dataset requires further investigation.

Prognostic role of plasma HER2 gene copy number in patients with HER2 positive metastatic breast cancer.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e13018-e13018 ◽  
Author(s):  
Ran Ran ◽  
Wenfa Huang ◽  
Shao Lin ◽  
Yunyun Niu ◽  
Hope S. Rugo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Metastatic Breast ◽  
Gene Copy ◽  
Prognostic Role ◽  
Her2 Gene ◽  
Her2 Positive

scholarly journals Pyrite oxidization accelerates bacterial carbon sequestration in copper mine tailings Type of contribution

2018 ◽  
Author(s):  
Yang Li ◽  
Zhaojun Wu ◽  
Xingchen Dong ◽  
Zifu Xu ◽  
Zhongjun Jia ◽  
...  
Keyword(s):  
Carbon Sequestration ◽  
Mine Tailings ◽  
Copy Number ◽  
Isotope Labeling ◽  
Gene Copy Number ◽  
Stable Isotope Probing ◽  
Gene Copy ◽  
Cbbl Gene ◽  
Heavy Fractions

Abstract. Polymetallic mine tailings have great potential as carbon sequestration tools to stabilize atmospheric CO2 concentrations. However, previous studies focused on carbonate mineral precipitation, while the role of autotrophs in carbon sequestration by mine tailings has been neglected. In this study, carbon sequestration in two mine tailings treated with FeS2 and 13C-labeled CO2 was analyzed using 13C isotope labeling, pyrosequencing and DNA-based stable isotope probing (SIP) to identify carbon fixers. Mine tailings treated with FeS2 exhibited a higher percentage of 13C atoms (1.76 ± 0.06 in Yangshanchong and 1.36 ± 0.01 in Shuimuchong) than the control groups over a 14-day incubation, as well an increase in the total organic carbon (TOC) content (0.20 ± 0.11 mg/g in Yangshanchong and 0.28 ± 0.14 mg/g in Shuimuchong). These data demonstrated the role of autotrophs in carbon sequestration with pyrite addition. Pyrite treatment led to changes in the composition of bacterial communities, and the genera Sulfobacillus (8.04 %) and Novosphingobium (8.60 %) were found to be dominant in these communities. In addition, the DNA-SIP results indicated that the cbbL gene copy number was 8.20–16.50 times greater than the cbbL gene copy number in 13C-labeled heavy fractions. Furthermore, a Sulfobacillus-like cbbL gene sequence (cbbL-OTU1) accounted for 30.11–34.74 % of all cbbL gene sequences in the 13C-labeled heavy fractions of mine tailings treated with FeS2. These findings highlight the importance of the RubisCO form I-encoding gene, cbbL, in bacterial carbon sequestration and demonstrate the ability of chemoautotrophs to sequester carbon during sulfide mineral oxidation in mine tailings. This study is the first to investigate carbon sequestration by autotrophic groups in mine tailings through the use of isotope tracers and DNA-SIP.

Prognostic role of PIK3CA and TP53 in human papillomavirus–negative oropharyngeal cancers

2018 ◽  
Vol 104 (3) ◽  
pp. 213-220 ◽  
Author(s):  
Carlo Resteghini ◽  
Federica Perrone ◽  
Rosalba Miceli ◽  
Cristiana Bergamini ◽  
Salvatore Alfieri ◽  
...  
Keyword(s):  
Functional Status ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Gene Gain ◽  
Fish Analysis ◽  
Prognostic Role ◽  
Pik3ca Gene ◽  
Pathologic Features

Background: Human papilloma virus (HPV)–negative oropharyngeal squamous cell carcinomas (OPCs) have a poorer prognosis and best management is an unmet need. We studied the prognostic role of epidermal growth factor receptor (EGFR) and PIK3CA amplifications and TP53 functional status. Methods: Between 1992 and 2000, 90 consecutive patients with OPCs were treated with surgery, followed by radiotherapy in case of high-risk pathologic features. Of those, 73 cases were HPV-negative and therefore were selected for molecular analysis ( PIK3CA and EGFR fluorescent in situ hybridization [FISH] analysis and TP53 mutation analysis). Results: FISH analyses of EGFR and PIK3CA were successfully conducted on 69 and 63 of 73 tumor samples, respectively. EGFR alterations were detected in 43% of patients but just 7% showed amplification. Seven cases (11%) carried PIK3CA amplification and 18 (29%) gene gain or high polysomy. TP53 was detected as nonfunctional in 24 of 67 (36%) successfully analyzed cases. Both univariable and multivariable analysis showed statistically significantly worse disease-free survival (DFS) for patients with PIK3CA disomy compared to those with gene gain or high polysomy. No differences in overall survival or DFS for EGFR and TP53 alteration were evident. The combined evaluation of PIK3CA and TP53 showed that PIK3CA gene copy number gain separated a population with better outcome, defining an overall worse prognosis population (disomy) now clearly further divided according to TP53 functional status. Conclusion: PIK3CA gene copy number increase is associated with a favorable clinical outcome in HPV-negative OPCs treated with surgery ± postoperative radiotherapy. In patients without PIK3CA alteration, TP53 nonfunctional mutations are associated with poor prognosis.

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