In silico studies of molecular alterations in fanconi anemia genes from cancer cell lines and samples

Authors

  • Jade Alexandra Silva Name
  • Victória Maria Ramos Salomão
  • Alexandre Moreira de Almeida
  • Renata Matuo
  • Fabrício Garmus Sousa

DOI:

https://doi.org/10.55905/oelv21n9-140

Keywords:

cellminercdb, drug activity, gene expression, fanconi anemia

Abstract

This paper proposes the use of bioinformatics tools to study the frequencies of alterations found in Fanconi Anemia (FA) genes, through cell lineage, drug activity (CellMinerCDB) in 4 databases (NCI-60, CCLE-Broad-MIT, GDSC-MGH-Sanger, and CTRP-Broad-MIT) evaluating expression, copy variation and mutation, and 32 cancer samples (cBioPortal) were analyzed, following the creation of genomic networks (Cytoscape). Results indicated FA genes with high mutation frequencies and with emphasis on the increase in gene copy gain. In cancer samples, a high frequency of mutations in uterine cancer in several FA genes was observed. Through network analysis, FANCI was correlated with molecular characteristics of repair pathways nominative as candidate for molecular markers and target uterine cancer therapies. Topoisomerases, Polo-Like-Kinases (PLK3), and Histone deacetylases (HDAC's) inhibitor drugs showed a significant P value in high correlations of several FA genes owing to copy gain, the expression these genes may be an important factor for anticancer treatment.

References

ANAND, P., et al. 2008. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res, 25, 2097-116.

BAHASSI EL, M., et al. 2002. Mammalian Polo-like kinase 3 (Plk3) is a multifunctional protein involved in stress response pathways. Oncogene, 21, 6633-40.

BASU, S., et al. 2017. Sparse network modeling and metscape-based visualization methods for the analysis of large-scale metabolomics data. Bioinformatics, 33, 1545-1553.

CATUCCI, I., et al. 2018. Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility. Genet Med, 20, 452-457.

CHENG, Y. & TIAN, H. 2017. Current Development Status of MEK Inhibitors. Molecules, 22.

CONCIN, N., et al. 2021. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer, 31, 12-39.

DEANS, A. J. & WEST, S. C. 2011. DNA interstrand crosslink repair and cancer. Nat Rev Cancer, 11, 467-80.

DEGENHARDT, Y. & LAMPKIN, T. 2010. Targeting Polo-like kinase in cancer therapy. Clin Cancer Res, 16, 384-9.

FEKAIRI, S., et al. 2009. Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases. Cell, 138, 78-89.

GOTTLICHER, M., et al. 2001. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J, 20, 6969-78.

GUEIDERIKH, A., et al. 2017. A never-ending story: the steadily growing family of the FA and FA-like genes. Genet Mol Biol, 40, 398-407.

HEVENER, K., et al. 2018. Recent developments in topoisomerase-targeted cancer chemotherapy. Acta Pharm Sin B, 8, 844-861.

HORN, L. C., et al. 2007. Histopathology of endometrial hyperplasia and endometrial carcinoma: an update. Ann Diagn Pathol, 11, 297-311.

JEGGO, P. A., et al. 2016. DNA repair, genome stability and cancer: a historical perspective. Nat Rev Cancer, 16, 35-42.

JEMAL, A., et al. 2011. Global cancer statistics. CA Cancer J Clin, 61, 69-90.

JOO, W., et al. 2011. Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway. Science, 333, 312-6.

JUNG, M., et al. 2020. Association of clinical severity with FANCB variant type in Fanconi anemia. Blood, 135, 1588-1602.

KAUR, J., et al. 2020. Association of XRCC1, XRCC2 and XRCC3 Gene Polymorphism with Esophageal Cancer Risk. Clin Exp Gastroenterol, 13, 73-86.

KIM, T. M., et al. 2011. The phenotype of FancB-mutant mouse embryonic stem cells. Mutat Res, 712, 20-7.

KRUPA, R., et al. 2011. Polymorphisms in RAD51, XRCC2 and XRCC3 genes of the homologous recombination repair in colorectal cancer--a case control study. Mol Biol Rep, 38, 2849-54.

LANDWEHR, R., et al. 2011. Mutation analysis of the SLX4/FANCP gene in hereditary breast cancer. Breast Cancer Res Treat, 130, 1021-8.

LYKO, F. 2018. The DNA methyltransferase family: a versatile toolkit for epigenetic regulation. Nat Rev Genet, 19, 81-92.

LYKO, F. & BROWN, R. 2005. DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J Natl Cancer Inst, 97, 1498-506.

MATHEW, C. G. 2006. Fanconi anaemia genes and susceptibility to cancer. Oncogene, 25, 5875-84.

MITO, K., et al. 2005. Expression of Polo-Like Kinase (PLK1) in non-Hodgkin's lymphomas. Leuk Lymphoma, 46, 225-31.

NEPAL, M., et al. 2017. FANCD2 and DNA Damage. Int J Mol Sci, 18.

NIRAJ, J., et al. 2019. The Fanconi Anemia Pathway in Cancer. Annu Rev Cancer Biol, 3, 457-478.

OHREN, J. F., et al. 2004. Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition. Nat Struct Mol Biol, 11, 1192-7.

OU, B., et al. 2019. Polo-like kinase 3 inhibits glucose metabolism in colorectal cancer by targeting HSP90/STAT3/HK2 signaling. J Exp Clin Cancer Res, 38, 426.

POMMIER, Y. 2006. Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer, 6, 789-802.

RAJAPAKSE, V. N., et al. 2018. CellMinerCDB for Integrative Cross-Database Genomics and Pharmacogenomics Analyses of Cancer Cell Lines. iScience, 10, 247-264.

SHAH, S., et al. 2013. Assessment of SLX4 Mutations in Hereditary Breast Cancers. PLoS One, 8, e66961.

SMITH, I. M., et al. 2010. Inactivation of the tumor suppressor genes causing the hereditary syndromes predisposing to head and neck cancer via promoter hypermethylation in sporadic head and neck cancers. ORL J Otorhinolaryngol Relat Spec, 72, 44-50.

SMOGORZEWSKA, A., et al. 2007. Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair. Cell, 129, 289-301.

SMOOT, M. E., et al. 2011. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics, 27, 431-2.

SONG, L., et al. 2021. The HDAC Inhibitor Domatinostat Promotes Cell-Cycle Arrest, Induces Apoptosis, and Increases Immunogenicity of Merkel Cell Carcinoma Cells. J Invest Dermatol, 141, 903-912 e4.

TERMINI L, VILLA L. Biomarcadores na triagem do câncer do colo uterino. J bras doenças sex transm. 2008;20(2):125-31.

WANG, Q., et al. 2002. Cell cycle arrest and apoptosis induced by human Polo-like kinase 3 is mediated through perturbation of microtubule integrity. Mol Cell Biol, 22, 3450-9.

WANG, Y., et al. 2018. Identification of a six-gene signature with prognostic value for patients with endometrial carcinoma. Cancer Med, 7, 5632-5642.

WILLERS, H., et al. 2008. Biomarkers and mechanisms of FANCD2 function. J Biomed Biotechnol, 2008, 821529.

WU, P., et al. 2019. Integration and Analysis of CPTAC Proteomics Data in the Context of Cancer Genomics in the cBioPortal. Mol Cell Proteomics, 18, 1893-1898.

YAN, Z., et al. 2010. A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability. Mol Cell, 37, 865-78.

YANG, Y., et al. 2008. Polo-like kinase 3 functions as a tumor suppressor and is a negative regulator of hypoxia-inducible factor-1 alpha under hypoxic conditions. Cancer Res, 68, 4077-85.

Downloads

Published

2023-09-26

How to Cite

Name, J. A. S., Salomão, V. M. R., de Almeida, A. M., Matuo, R., & Sousa, F. G. (2023). In silico studies of molecular alterations in fanconi anemia genes from cancer cell lines and samples. OBSERVATÓRIO DE LA ECONOMÍA LATINOAMERICANA, 21(9), 13067–13087. https://doi.org/10.55905/oelv21n9-140

Issue

Vol. 21 No. 9 (2023)

Section

Articles

License

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.