Acta Scientific Cancer Biology (ASCB) (ISSN: 2582-4473)

Research Article Volume 7 Issue 8

BRCA1/2-mutant Breast Cancer: Genome-Wide Comparative Analysis, Differentially Expressed Genes and Key Molecules Analyze by Evidence from Bioinformatics Analyses

Ghania Qindeel*, Quratulain, Nubla Batool and Sheraz Akmal

Government College University, Lahore, Pakistan

*Corresponding Author: Ghania Qindeel, Government College University, Lahore, Pakistan.

Received: August 17, 2023; Published: September 06, 2023

Abstract

The BRCA1 and BRCA2 genes have been linked to a higher risk of breast cancer throughout a person's lifespan. BRCA1/2 mutations in breast cancer have yet to be thoroughly characterized in terms of the genes that are closely linked to those alterations. This project seeks to discover gene expression interaction and patterns networks affected by BRCA1/2 mutations, to represent underlying disease processes and provide novel biomarkers for breast cancer diagnosis or prognosis. The advancement of molecular genetics in recent years has improved our understanding of the concepts of breast cancer development. This study is accomplished to understand genomic variations and for sequence analysis. Freely accessible online tools such as pfam, GSDS (gene structure display server), SMART, STRING 9.1, PTMcode 2,PDB, MEME motif, CLUSTAL W, Serial Cloner and Mega X were used to perform sequence and mutational analysis. The Cancer Genome Atlas (TCGA), gene expression profiles were obtained and integrated with the cBioPortal website to identify specific breast cancer patients with BRCA1/2 mutations, according to the study. Using gene set enrichment analysis (GSEA), certain enriched pathways and biochemical characteristics linked with BRCA mutations were identified and characterized. Three separate differentially expressed genes (DEGs) analyses were done for BRCA1/2-mutant breast cancer, wild-type breast cancer, and the matching normal tissues to validate putative hub genes with each other. Key genes linked with BRCA1/2 mutations were identified using protein-protein interaction networks (PPI), survival analysis, and diagnostic value evaluation. Taken together, our findings shed light on specific mutations and proteins implicated in the interaction network of BRCA1 and BRCA2, which may play similar roles in breast cancer. However, the complicated process behind these results has yet to be fully explained, and further research is needed in the future.

 Keywords: Mutations; BRCA; Biomarkers; Bioinformatics

References

  1. Miki Yoshio., et al. "A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1”. Science5182 (1994): 66-71.
  2. Li Yue., et al. "Differentially expressed genes and key molecules of BRCA1/2-mutant breast cancer: evidence from bioinformatics analyses”. Peer Journal8 (2020): e8403.
  3. Wooster Richard., et al. "Identification of the breast cancer susceptibility gene BRCA2”. Nature6559 (1995): 789-792.
  4. Antoniou Antonis C., et al. "Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies”. Journal of Medical Genetics7 (2005): 602-603.
  5. Chen Sining and Giovanni Parmigiani. "Meta-analysis of BRCA1 and BRCA2 penetrance”. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology11 (2007): 1329.
  6. Mavaddat Nasim., et al. "Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE”. JNCI: Journal of the National Cancer Institute11 (2013): 812-822.
  7. Wooster Richard., et al. "Identification of the Breast-Cancer Susceptibility Gene BRCA2 (Vol 378, Pg 789, 1995)”. Nature6567 (1996): 749-749.
  8. Chapman Mark S and Inder M Verma. "Transcriptional activation by BRCA1”. Nature6593 (1996): 678-679.
  9. Kolinjivadi Arun Mouli., et al. "Moonlighting at replication forks–a new life for homologous recombination proteins BRCA 1, BRCA 2 and RAD 51”. FEBS Letters8 (2017): 1083-1100.
  10. Chen Junjie., et al. "Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells”. Molecular Cell3 (1998): 317-328.
  11. Rebbeck Timothy R., et al. "Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations”. Human Mutation5 (2018): 593-620.
  12. Smith SA., et al. "Allele losses in the region 17q12–21 in familial breast and ovarian cancer involve the wild–type chromosome”. Nature Genetics2 (1992): 128-131.
  13. Thull Darcy L and Victor G Vogel. "Recognition and management of hereditary breast cancer syndromes”. The Oncologist1 (2004): 13-24.
  14. Alvarez Carolina., et al. "Different Array CGH profiles within hereditary breast cancer tumors associated to BRCA1 expression and overall survival”. Bmc Cancer1 (2016): 1-14.
  15. Wang Zhu., et al. "Expression and mutations of BRCA in breast cancer and ovarian cancer: Evidence from bioinformatics analyses”. International Journal of Molecular Medicine6 (2018): 3542-3550.
  16. Lee Megan S., et al. "Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays”. Cancer Research12 (2010): 4880-4890.
  17. Monteiro Alvaro N., et al. "Variants of uncertain clinical significance in hereditary breast and ovarian cancer genes: best practices in functional analysis for clinical annotation”. Journal of Medical Genetics8 (2020): 509-518.
  18. Guidugli Lucia., et al. "A classification model for BRCA2 DNA binding domain missense variants based on homology-directed repair activity”. Cancer Research1 (2013): 265-275.
  19. Carlsson Jonas Thierry Soussi and Bengt Persson. "Investigation and prediction of the severity of p53 mutants using parameters from structural calculations”. The FEBS journal15 (2009): 4142-4155.
  20. Ismaeel Ayad Ghany. "New Approach for Prediction Pre-cancer via Detecting Mutated in Tumor Protein P53”. arXiv preprint arXiv:1310.2182 (2013).
  21. Ismaeel Ayad Ghany and Anar Auda Ablahad. "Novel method for mutational disease prediction using bioinformatics techniques and backpropagation algorithm”. arXiv preprint arXiv:1303.0539 (2013).
  22. Kharya Shweta. "Using data mining techniques for diagnosis and prognosis of cancer disease”. arXiv preprint arXiv:1205.1923 (2012).
  23. Claverie Jean-Michel and Cedric Notredame. Bioinformatics for dummies. John Wiley and Sons (2006).
  24. Deepa R., et al. "Bio-Microbe Analyst: New-Fangled Unambiguous Syndrome Prediction to Classify Cancer with Recent Computational Gist” (2013).

Citation

Citation: Ghania Qindeel., et al.BRCA1/2-mutant Breast Cancer: Genome-Wide Comparative Analysis, Differentially Expressed Genes and Key Molecules Analyze by Evidence from Bioinformatics Analyses" Acta Scientific Cancer Biology 7.8 (2023): 08-21.

Copyright

Copyright: © 2023 Ghania Qindeel., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.




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Acceptance rate35%
Acceptance to publication20-30 days
Impact Factor1.183

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