Total copy number variation, somatic mutation burden, and histologic grade correlate with clinical outcome in oligodendroglioma

e23190 Background: Survival time among esophageal cancer patients undergoing radiotherapy varies considerably. Treatment failure resulting from local recurrence and metastasis reflects varying biological features such as radiosensitivity, invasion, and metastasis. This study aims to explore the genetic characterizations that are associated with prognosis of esophageal cancer patients who have undergone radiotherapy. Methods: We retrospectively reviewed specimens of 21 patients who were treated with radiotherapy. Based on the progression-free-survival (PFS), these patients were divided in to two groups: short PFS group with an average PFS of 6.9 months and long PFS group with an average PFS of 31.9 months. We extracted DNA from paraffin specimens for next generation sequencing. Mutation burden (the sum of mutation frequencies of targeted genes) and copy number aberrance were analyzed by targeted sequencing that covers 1086 genes. Results: We excluded six samples in the mutation burden analysis because of the shortage of coverage of the targeted genes. The mutation burden of 15 genes panel, which included ARID1A, BCL2, BRAF, CDH1, ERBB2, FAT1, LRP1B, MET, MTOR, NOTCH1,NOTCH2, PDGFRA, PTCH1, RB1, STK11, showed a statistically significant difference between the long PFS group and the short PFS group (p value = 0.001408). We then used copy number variation (CNV) kit to detect genes copy number variation between these two groups. The CNV of 9 genes panel, which include ASH1L, CD55, CDK4, CREBBP, FGFR1, MYC, TP53 , TYMS, XRCC3, showed a statistically significant difference between the long PFS group and the short PFS group (p value = 0.03147). Conclusions: Our results suggested that the gene mutation burden and CNV detected by targeted sequencing have a relationship with the prognosis of esophageal cancer patients who had undergone radiotherapy. In this exploratory study, we involved patients with extreme PFS ( < 1 year and > 2 years), which can be expanded in the future. To construct a predictive genetic model of prognosis in esophageal cancer patients, one may also consider analyzing circulating tumor DNA (ctDNA) in serum.

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Genomic copy number variation associated with clinical outcome in canine cutaneous mast cell tumors

Research in Veterinary Science ◽

10.1016/j.rvsc.2016.11.009 ◽

2017 ◽

Vol 111 ◽

pp. 26-30 ◽

Cited By ~ 5

Author(s):

Paulo C Jark ◽

Deborah B.P. Mundin ◽

Marcio de Carvalho ◽

Raquel B. Ferioli ◽

Letícia A Anai ◽

...

Keyword(s):

Mast Cell ◽

Clinical Outcome ◽

Copy Number Variation ◽

Copy Number ◽

Genomic Copy Number ◽

Mast Cell Tumors ◽

Genomic Copy ◽

Number Variation ◽

Cutaneous Mast Cell ◽

Genomic Copy Number Variation

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Integrated Analysis of Copy Number Variation, Microsatellite Instability, and Tumor Mutation Burden Identifies an 11-Gene Signature Predicting Survival in Breast Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.721505 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xin Jin ◽

Junfeng Yan ◽

Chuanzhi Chen ◽

Yi Chen ◽

Wen-Kuan Huang

Keyword(s):

Breast Cancer ◽

Copy Number Variation ◽

Genetic Variants ◽

Copy Number ◽

Risk Model ◽

Gene Signature ◽

Integrated Analysis ◽

Tumor Mutation Burden ◽

Mutation Burden ◽

Number Variation

Genetic variants such as copy number variation (CNV), microsatellite instability (MSI), and tumor mutation burden (TMB) have been reported to associate with the immune microenvironment and prognosis of patients with breast cancer. In this study, we performed an integrated analysis of CNV, MSI, and TMB data obtained from The Cancer Genome Atlas, thereby generating two genetic variants-related subgroups. We characterized the differences between the two subgroups in terms of prognosis, MSI burden, TMB, CNV, mutation landscape, and immune landscape. We found that cluster 2 was marked by a worse prognosis and lower TMB. According to these groupings, we identified 130 differentially expressed genes, which were subjected to univariate and least absolute shrinkage and selection operator-penalized multivariate modeling. Consequently, we constructed an 11-gene signature risk model called the genomic variation-related prognostic risk model (GVRM). Using ROC analysis and a calibration plot, we estimated the prognostic prediction of this GVRM. We confirmed the predictive efficiency of this GVRM by validating it in another independent International Cancer Genome Consortium cohort. Our results conclude that an 11-gene signature developed by integrated analysis of CNV, MSI, and TMB has a high potential to predict breast cancer prognosis, which provided a strong rationale for further investigating molecular mechanisms and guiding clinical decision-making in breast cancer.

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Identification of mutated core cancer modules by integrating somatic mutation, copy number variation, and gene expression data

BMC Systems Biology ◽

10.1186/1752-0509-7-s2-s4 ◽

2013 ◽

Vol 7 (Suppl 2) ◽

pp. S4 ◽

Cited By ~ 19

Author(s):

Junhua Zhang ◽

Shihua Zhang ◽

Yong Wang ◽

Xiang-Sun Zhang

Keyword(s):

Gene Expression ◽

Copy Number Variation ◽

Somatic Mutation ◽

Gene Expression Data ◽

Copy Number ◽

Expression Data ◽

Number Variation

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Total copy number variation as a prognostic factor in adult astrocytoma subtypes

Acta Neuropathologica Communications ◽

10.1186/s40478-019-0746-y ◽

2019 ◽

Vol 7 (1) ◽

Cited By ~ 11

Author(s):

Kanish Mirchia ◽

Adwait Amod Sathe ◽

Jamie M. Walker ◽

Yelena Fudym ◽

Kristyn Galbraith ◽

...

Keyword(s):

Prognostic Factor ◽

Copy Number Variation ◽

Copy Number ◽

Number Variation ◽

Total Copy Number

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Somatic mutation and copy number variation associated with malignant transformation of IPMN detected by next-generation sequencing

Pancreatology ◽

10.1016/j.pan.2016.06.261 ◽

2016 ◽

Vol 16 (4) ◽

pp. S72

Author(s):

Shinichi Takano ◽

Mitsuharu Fukasawa ◽

Makoto Kadokura ◽

Hiroko Shindo ◽

Ei Takahashi ◽

...

Keyword(s):

Next Generation Sequencing ◽

Copy Number Variation ◽

Malignant Transformation ◽

Somatic Mutation ◽

Copy Number ◽

Next Generation ◽

Number Variation ◽

Generation Sequencing

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The prognostic values and clinical implications of m6A methylation regulators in epithelial ovarian cancer

10.21203/rs.3.rs-17066/v1 ◽

2020 ◽

Author(s):

huimin shen ◽

Tiefeng Cao ◽

Jinhui Li

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Clinical Outcome ◽

Copy Number Variation ◽

Epithelial Ovarian Cancer ◽

Copy Number ◽

Regulatory Gene ◽

Disease Free Survival ◽

Regulatory Genes ◽

Number Variation

Abstract Background: N6-methyladenosine (m6A) exists in both DNA and RNA modification. RNA m6A modification drives tumor initiation and metastasis through regulating cancer stem cells. However, the detailed mechanisms and the distinct m6A regulatory gene type underlying ovarian cancer mRNA modification remain unclear. Results: We analyzed copy number variation (CNVs) and mRNA expression of ovarian cancer cases in TCGA dataset to determine the copy number variation patterns of m6A regulatory genes, and the associations between m6A dysregulation or certain regulatory gene and overall survival. We showed the KIAA1429, as the writer gene, had highest amplification percentage and were associated with overall survival, or disease-free survival, whereas the associations with prognostic survival were independent of other prognostic factors including stage, grade, and debulking status of the tumour. Besides, METTL14 and YTHDC2, one as the writer gene and the other as reader gene, was also related with clinical outcome. Furthermore, subgroups analysis addressed that m6A upregulation especially writer gain contributed to prognosis in epithelial ovarian cancer. Conclusions: Collectively, our data addressed that m6A upregulation is likely to be critical to the clinical outcome, and KIAA1429 showed the highest correlation with clinical outcome in ovarian cancer among m6A regulatory genes.

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The mutational landscape of MSI-H and MSS colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15122 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15122-e15122

Author(s):

Enxiao LI ◽

Ying Hu ◽

Wenbo Han ◽

Tianshu Liu ◽

Fang Lv ◽

...

Keyword(s):

Colorectal Cancer ◽

Copy Number Variation ◽

Microsatellite Instability ◽

Copy Number ◽

Mononucleotide Repeat ◽

Tumor Mutation Burden ◽

Mutational Landscape ◽

Mutation Burden ◽

Keywords Colorectal Cancer ◽

Number Variation

e15122 Background: The microsatellite instability-high (MSI-H) phenotype confers good prognosis and greater response to immunotherapy in colorectal cancer(CRC). The mutational landscape of MSI-H CRC is unclear. This study was designed to illustrate the difference mutation profile between the MSI-H and microsatellite stable (MSS) CRC. Methods: Tumor tissue and matched blood samples from 40 patients with colorectal cancer were collected. Microsatellite instability (MSI) status were detected by PCR-amplified for five mononucleotide repeat markers (BAT-25, BAT-26, NR-21, NR-24 and MONO-27). Mutation profiles were sequenced by a cancer gene-targeted NGS panel. Results: The tumor mutation burden(TMB) of the MSI-H CRC patients was significantly higher than those MSS CRC patients. Compared with the MSS CRC, MSI-H CRC involved more genes and pathways. Furthermore, we found the copy number variation (CNV) was different between the two groups. The copy number instability (CNI) score of MSI-H CRC patients was significantly lower than those MSS CRC patients. MSI-H CRC patients showed a higher frequency of TP53 gene CNV gain compared with MSS CRC (41% (7/17) in MSI-H CRC versus 13% (3/23) in MSS CRC). Conclusions: The mutational landscape are different between the MSI-H and MSS colorectal cancer. Compared with MSS colorectal cancer, the MSI-H colorectal cancer patients have higher tumor mutation burden(TMB) and lower copy number instability (CNI) score. Keywords: colorectal cancer, microsatellite instability, tumor mutation burden, copy number instability. Abbreviations CRC, colorectal cancer; TMB, tumor mutation burden; MSI-H, The microsatellite instability-high; MSS, microsatellite stable; CNV, copy number variation.

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