Role of Rare Germline Copy Number Variation in Melanoma-Prone Patients

Fidalgo, Felipe; Rodrigues, T.; Silva, Amanda Gonçalves; Facure, Luciana; Sá, Bianca Costa Soares de; Duprat, João Pedreira; Achatz, Maria Isabel; Rosenberg, Carla; Carraro, Dirce Maria; Krepischi, Ana Cristina Victorino

doi:10.2217/fon.16.22

Cited by 9 publications

(8 citation statements)

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“…Previous studies revealed that histone family genes are involved in multiple cancer types. Copy number variations of HIST1H1B were reported to be associated with cellular development and growth, and with proliferation in melanoma (30). HIST1H3B , as an amplification-dependent driver oncogene, was reported to be overexpressed in liver cancer (31).…”

Section: Discussionmentioning

confidence: 99%

Expression and potential prognostic value of histone family gene signature in breast cancer

et al. 2019

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Breast cancer (BC) is the most common type of malignancy among females worldwide. Histone modifications, which are the major post-translational modifications, have a significant role in cancer development and prognosis. However, whether histone family genes may serve as potential prognostic biomarkers for BC patients has remained elusive. In the present study, RNA-sequencing data were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed genes were identified and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway functional enrichment analysis was performed. As histone family genes have been reported to be associated with cervical cancer, the present study hypothesized that histone family genes are associated with gynecological tumors. Histone family genes, including histone cluster 1 H1A family member B (HIST1H1B), HIST1H2AJ, HIST1H2AM, HIST1H2BI, HIST1H2BO, HIST1H3B, HIST1H3F, HIST1H3H, HIST1H4C and HIST1H4D, were upregulated and identified as hub genes in the protein-protein interaction network. In addition, Oncomine and the Human Protein Atlas were used to further verify the expression levels of histone gene sets. The PrognoScan database was then used to investigate the association between expression and prognostic value regarding cancer patient survival. The present results indicated that higher expression of histone gene sets was associated with poor overall survival, relapse-free survival and distant metastasis-free survival of BC patients. The differential expression of histone family genes between BC and normal samples was validated by reverse transcription-quantitative PCR. Finally, to determine the clinical role of histone family genes in BC, the correlations between histone family genes expression and clinical characteristics were investigated through data collected from TCGA. Therefore, the present study indicates that histone gene sets may be used as prognostic factors for survival prediction for BC patients.

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Section: Discussionmentioning

confidence: 99%

Expression and potential prognostic value of histone family gene signature in breast cancer

et al. 2019

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“…In this workflow, the gene list submitted to VarElect includes genes residing (completely or partially) within the detected SVs. This mode of analysis using VarElect helped solve a number of cases (Homma et al 2018;Fidalgo et al 2016). One study aimed to diagnose recurrent CNVs associated with syndromic short stature of unknown cause (Homma et al 2018).…”

Section: Interpretation Of Genomic Structural Variants (Svs)mentioning

confidence: 99%

The GeneCards Suite

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et al. 2021

Practical Guide to Life Science Databases

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The GeneCards® database of human genes was launched in 1997 and has expanded since then to encompass gene-centric, disease-centric, and pathway-centric entities and relationships within the GeneCards Suite, effectively navigating the universe of human biological data—genes, proteins, cells, regulatory elements, biological pathways, and diseases—and the connections among them. The knowledgebase amalgamates information from >150 selected sources related to genes, proteins, ncRNAs, regulatory elements, chemical compounds, drugs, splice variants, SNPs, signaling molecules, differentiation protocols, biological pathways, stem cells, genetic tests, clinical trials, diseases, publications, and more and empowers the suite’s Next Generation Sequencing (NGS), gene set, shared descriptors, and batch query analysis tools.

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“…Germline CNVs are a class of structural variations, and are defined as loss or gain of genomic DNA in size range of 50 bp to 1 Mb 14 . Germline CNVs are studied as genetic determinants for susceptibility for familial breast cancer 15 – 20 and also cancers of prostate 21 – 23 , ovary 18 , 24 – 26 , pancreas 27 – 29 , colon, rectum 16 , 30 – 34 , endometrium 35 , lung 36 – 38 and melanoma 39 , 40 .…”

Section: Introductionmentioning

confidence: 99%

Germline copy number variations are associated with breast cancer risk and prognosis

Kumaran

Cass

Graham

et al. 2017

Sci Rep

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Breast cancer is one of the most common cancers among women, and susceptibility is explained by genetic, lifestyle and environmental components. Copy Number Variants (CNVs) are structural DNA variations that contribute to diverse phenotypes via gene-dosage effects or cis-regulation. In this study, we aimed to identify germline CNVs associated with breast cancer susceptibility and their relevance to prognosis. We performed whole genome CNV genotyping in 422 cases and 348 controls using Human Affymetrix SNP 6 array. Principal component analysis for population stratification revealed 84 outliers leaving 366 cases and 320 controls of Caucasian ancestry for association analysis; CNVs with frequency > 10% and overlapping with protein coding genes were considered for breast cancer risk and prognostic relevance. Coding genes within the CNVs identified were interrogated for gene-dosage effects by correlating copy number status with gene expression profiles in breast tumor tissue. We identified 200 CNVs associated with breast cancer (q-value < 0.05). Of these, 21 CNV regions (overlapping with 22 genes) also showed association with prognosis. We validated representative CNVs overlapping with APOBEC3B and GSTM1 genes using the TaqMan assay. Germline CNVs conferred dosage effects on gene expression in breast tissue. The candidate CNVs identified in this study warrant independent replication. Breast Cancer is one of the commonly diagnosed cancers among women worldwide 1 , in Canada, breast cancer accounts for about 25% of all diagnosed cancers, and 15% of all cancer deaths 2 . Based on twin studies, estimated heritable genetic factors contribute to about 30% for breast cancer risk, the remaining risk being due to environmental and lifestyle factors 3 . Family based linkage and genome sequencing studies have identified high and moderate penetrant mutations in genes such as BRCA 1 or BRCA 2 4,5 PTEN 6 , PALB2 7 , ATM 8 , TP53 9 , and CHECK2 10 that contribute to the genetic risk of breast cancers. Subsequently, large scale population based Genome Wide Association Studies (GWAS) were successful in identifying several low penetrant common genetic variants (Single Nucleotide Polymorphisms, SNPs) associated with breast cancer risk. Among these, a limited number of GWAS SNPs (7 SNPs) showed effect sizes (odds ratio or ORs) between 1.25-1.5 and the remaining SNPs showed effect sizes < 1.25 11,12 . SNP based GWAS served as a valuable tool in uncovering novel genes or loci associated with breast cancer aetiology. Low, moderate and high penetrant SNPs and mutations together explain up to 50% of the genetic risk associated with breast cancer 11,12 , and the remaining variants to explain the "missing heritability" are yet to be discovered. Copy Number Variations (CNVs) in the germline DNA are currently being investigated to explain missing heritable risk for breast cancer 13 . Germline CNVs are a class of structural variations, and are defined as loss or gain of genomic DNA in size range of 50 bp to 1 Mb 14 . Germline CNVs are studied as ...

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Role of Rare Germline Copy Number Variation in Melanoma-Prone Patients

Abstract: Patients harboring rare CNVs exhibited a decreased age of disease onset, in addition to an overall higher skin cancer predisposition. Our findings suggest that rare CNVs contribute to melanoma susceptibility, and should be taken into account when investigating cancer risk factors.

Cited by 9 publications

References 53 publications

Expression and potential prognostic value of histone family gene signature in breast cancer

Expression and potential prognostic value of histone family gene signature in breast cancer

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Germline copy number variations are associated with breast cancer risk and prognosis

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