Analysis of TGCA data reveals genetic and epigenetic changes and biological function of MUC family genes in colorectal cancer

Aim: Few studies focused on functions and regulatory networks of MUC family members in colorectal cancer based on comprehensive analysis of online database. Materials & methods: Copy number variation, methylation, pathway analysis and drug influence on MUC expression were analyzed based on The Cancer Genome Atlas and GTEx database. Results: Copy number variation analysis showed MUC heterozygous amplification and heterozygous deletion predominate. Methylation of MUC17, MUC12 and MUC4 were found related to gene expression. Function of MUC family genes mainly affects pathways such as apoptosis, cell cycle, DNA damage and EMT pathways. PLX4720, dabrafenib, gefitinib, afatinib and austocystin D can alter the expression of MUC gene. Conclusion: The genetic and epigenetic changes of MUC are related to the level of MUC expression in colorectal cancer.

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Inferring Homologous Recombination Deficiency of Ovarian Cancer From the Landscape of Copy Number Variation at Subchromosomal and Genetic Resolutions

Frontiers in Oncology ◽

10.3389/fonc.2021.772604 ◽

2021 ◽

Vol 11 ◽

Author(s):

Meng Zhang ◽

Si-Cong Ma ◽

Jia-Le Tan ◽

Jian Wang ◽

Xue Bai ◽

...

Keyword(s):

Ovarian Cancer ◽

Homologous Recombination ◽

Copy Number Variation ◽

Copy Number ◽

The Cancer Genome Atlas ◽

Homologous Recombination Deficiency ◽

Number Variation ◽

Cancer Genome Atlas ◽

Tumor Types ◽

Pan Cancer

BackgroundHomologous recombination deficiency (HRD) is characterized by overall genomic instability and has emerged as an indispensable therapeutic target across various tumor types, particularly in ovarian cancer (OV). Unfortunately, current detection assays are far from perfect for identifying every HRD patient. The purpose of this study was to infer HRD from the landscape of copy number variation (CNV).MethodsGenome-wide CNV landscape was measured in OV patients from the Australian Ovarian Cancer Study (AOCS) clinical cohort and >10,000 patients across 33 tumor types from The Cancer Genome Atlas (TCGA). HRD-predictive CNVs at subchromosomal resolution were identified through exploratory analysis depicting the CNV landscape of HRD versus non-HRD OV patients and independently validated using TCGA and AOCS cohorts. Gene-level CNVs were further analyzed to explore their potential predictive significance for HRD across tumor types at genetic resolution.ResultsAt subchromosomal resolution, 8q24.2 amplification and 5q13.2 deletion were predominantly witnessed in HRD patients (both p < 0.0001), whereas 19q12 amplification occurred mainly in non-HRD patients (p < 0.0001), compared with their corresponding counterparts within TCGA-OV. The predictive significance of 8q24.2 amplification (p < 0.0001), 5q13.2 deletion (p = 0.0056), and 19q12 amplification (p = 0.0034) was externally validated within AOCS. Remarkably, pan-cancer analysis confirmed a cross-tumor predictive role of 8q24.2 amplification for HRD (p < 0.0001). Further analysis of CNV in 8q24.2 at genetic resolution revealed that amplifications of the oncogenes, MYC (p = 0.0001) and NDRG1 (p = 0.0004), located on this fragment were also associated with HRD in a pan-cancer manner.ConclusionsThe CNV landscape serves as a generalized predictor of HRD in cancer patients not limited to OV. The detection of CNV at subchromosomal or genetic resolution could aid in the personalized treatment of HRD patients.

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Chromosome Copy Number Variation Analysis to Detect Early Colorectal Cancer With Liquid Biopsy

Clinical Gastroenterology and Hepatology ◽

10.1016/j.cgh.2016.09.113 ◽

2017 ◽

Vol 15 (1) ◽

pp. e47 ◽

Cited By ~ 1

Author(s):

Jun-feng Xu ◽

Lang Yang ◽

Xing-yong Ma ◽

Qian Kang ◽

Peng Jin ◽

...

Keyword(s):

Colorectal Cancer ◽

Copy Number Variation ◽

Liquid Biopsy ◽

Copy Number ◽

Early Colorectal Cancer ◽

Variation Analysis ◽

Chromosome Copy Number ◽

Copy Number Variation Analysis ◽

Number Variation ◽

Chromosome Copy Number Variation

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Characterization of TERT and BRAF copy number variation in papillary thyroid carcinoma: An analysis of the cancer genome atlas study

Genes Chromosomes and Cancer ◽

10.1002/gcc.22928 ◽

2020 ◽

Author(s):

Brittany A. McKelvey ◽

Martha A. Zeiger ◽

Christopher B. Umbricht

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Copy Number Variation ◽

Copy Number ◽

The Cancer Genome Atlas ◽

Papillary Thyroid ◽

Number Variation ◽

Cancer Genome Atlas ◽

Genome Atlas

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Validation of copy number variation analysis for next-generation sequencing diagnostics

European Journal of Human Genetics ◽

10.1038/ejhg.2017.42 ◽

2017 ◽

Vol 25 (6) ◽

pp. 719-724 ◽

Cited By ~ 42

Author(s):

Jamie M Ellingford ◽

Christopher Campbell ◽

Stephanie Barton ◽

Sanjeev Bhaskar ◽

Saurabh Gupta ◽

...

Keyword(s):

Next Generation Sequencing ◽

Copy Number Variation ◽

Copy Number ◽

Variation Analysis ◽

Next Generation ◽

Copy Number Variation Analysis ◽

Number Variation ◽

Generation Sequencing

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EPCO-28. SINGLE-CELL RNA SEQUENCING IDENTIFIES INTRATUMORAL HETEROGENEITY AND ACTIVATION OF PRO-INVASIVE PATHWAYS IN NON-FUNCTIONING PITUITARY ADENOMAS

Neuro-Oncology ◽

10.1093/neuonc/noab196.027 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi8-vi8

Author(s):

Saket Jain ◽

Elaina Wang ◽

Husam Babikir ◽

Karin Shamardani ◽

Aaron Diaz ◽

...

Keyword(s):

Copy Number Variation ◽

Wnt Signaling ◽

Single Cell ◽

Rna Sequencing ◽

Pituitary Adenomas ◽

Copy Number ◽

Variation Analysis ◽

Copy Number Variation Analysis ◽

Single Cell Rna Sequencing ◽

Number Variation

Abstract Pituitary adenomas (PA) are one of the most common primary brain tumors and comprise 15% of brain neoplasms. Most PAs are histologically benign but can cause significant morbidity. The genetic profile of PAs is poorly understood. We used single-cell RNA sequencing using the 10X genomic platform to investigate cellular heterogeneity in twelve non-functioning pituitary adenoma samples from nine patients including site-specific (core vs edge) samples from three patients. Our analysis identified discrete clusters of cells associated with activation of specific functional pathways including lipid metabolism, angiogenic, and antigen presentation and processing pathways regardless of location within the tumor. MALT1, a lncRNA associated with increased proliferation and metastasis was ubiquitously expressed amongst these samples. Analysis of the core vs edge samples showed two specific clusters with activated invasion-promoting pathways including PI3k/AKT signaling, Wnt signaling (Wnt6 and FZD4), and epithelial-mesenchymal transition (TGFB1, SMAD1, ZEB1, and SNAI2) in the edge of the tumors. The activated Wnt signaling cascade drove a proinflammatory tumor microenvironment induced by the expression of IL-1, IL-17, and Toll-like receptors (TLR6 and TLR7/8) resulting in suppression of Tregs. Copy number variation analysis using the CONICS-CNV algorithm highlighted distinct chromosomal alterations within our samples that led to insight into clonal variations within each tumor with loss of chromosome 2 an early event in tumorigenesis and gain/loss of chromosome 19 as late events. Mapping the copy number variation analysis with the somatic variant analysis using the Vartrix algorithm identified novel driver mutations within these tumors. These findings help define the molecular fingerprint of pituitary adenomas and provide insights which could be utilized for better management of these tumors.

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