Novel Nonsense Variants c.58C&gt;T (p.Q20X) and c.256G&gt;T (p.E85X) in the CHEK2 Gene Identified dentified in Breast Cancer Patients from Balochistan

Baloch, Abdul Hameed; Khosa, Ahmad Nawaz; Bangulzai, Nasrullah; Shuja, Jamila; Naseeb, Hafiz Khush; Jan, Mohammed M.; Marghazani, Illahi Bakhsh; Kakar, Masood-ul Haq; Baloch, Dost Muhammad; Cheema, Abdul Majeed; Ahmad, Jamil

doi:10.7314/apjcp.2016.17.3.1089

Cited by 5 publications

(4 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides the well-known and most studied mutations described previously, others have been reported, such as Q20X and E85X mutations at exons 1 and 2, respectively, which are novel and have been identified in breast cancer patients from Pakistan 29. Previous experimental data on the same area suggested that two additional missense mutations (H371Y and D438Y) are also associated with breast cancer in women 30.…”

Section: Other Mutationsmentioning

confidence: 88%

Current perspectives on CHEK2 mutations in breast cancer

Apostolou¹,

Papasotiriou²

2017

BCTT

View full text Add to dashboard Cite

Checkpoint kinase 2 (CHEK2) is a serine/threonine kinase which is activated upon DNA damage and is implicated in pathways that govern DNA repair, cell cycle arrest or apoptosis in response to the initial damage. Loss of kinase function has been correlated with different types of cancer, mainly breast cancer. CHEK2 functionality is affected by different missense or deleterious mutations. CHEK2*1100delC and I157T are most studied in populations all over the world. Although these variants have been identified in patients with breast cancer, their frequency raises doubts about their importance as risk factors. The present article reviews the recent advances in research on CHEK2 mutations, focusing on breast cancer, based on the latest experimental data.

show abstract

Section: Other Mutationsmentioning

confidence: 88%

Current perspectives on CHEK2 mutations in breast cancer

Apostolou¹,

Papasotiriou²

2017

BCTT

View full text Add to dashboard Cite

show abstract

“…The individual having CHK2 sequence variants (c.1100delC) may contribute to the Li-Fraumeni syndrome in Dutch families [60]. In Pakistan, two novel mutations p.Gln20X and p.Glu85X at exons 1 and 2 respectively have been identified in breast cancer patients [61]. However the results were contradictory among different studies.…”

Section: Discussionmentioning

confidence: 99%

Computational analysis of high-risk SNPs in human CHK2 gene responsible for hereditary breast cancer: A functional and structural impact

2019

View full text Add to dashboard Cite

Nowadays CHK2 mutation is studied frequently in hereditary breast and ovarian cancer patients in addition to BRCA1/BRCA2. CHK2 is a tumor suppressor gene that encodes a serine/threonine kinase, also involved in pathways such as DNA repair, cell cycle regulation and apoptosis in response to DNA damage. CHK2 is a well-studied moderate penetrance gene that correlates with third high risk susceptibility gene with an increased risk for breast cancer. Hence before planning large population study, it is better to scrutinize putative functional SNPs of CHK2 using different computational tools. In this study, we have used various computational approaches to identify nsSNPs which are deleterious to the structure and/or function of CHK2 protein that might be causing this disease. Computational analysis was performed by different in silico tools including SIFT, Align GVGD, SNAP-2, PROVEAN, Poly-Phen-2, PANTHER, PhD-SNP, MUpro, iPTREE-STAB, Consurf, InterPro, NCBI Conserved Domain Search tool, ModPred, SPARKS-X, RAMPAGE, Verify-3D, FT Site, COACH and PyMol. Out of 78 nsSNP of human CHK2 gene, seven nsSNPs were predicted functionally most significant SNPs. Among these seven nsSNP, p.Arg160Gly, p.Gly210Arg and p.Ser415Phe are highly conserved residues with conservation score of 9 and three nsSNP were predicted to be involved in post translational modification. The p.Arg160Gly and p.Gly210Arg may interfere in phosphopeptide binding site on FHA conserved domain. The p.Ser415Phe may interfere in formation of activation loop of protein-kinase domain and might interfere in interactions of CHK2 with ligand. The study concludes that mutation of serine to phenylalanine at position 415 is a major mutation in native CHK2 protein which might contribute to its malfunction, ultimately causing disease. This is the first comprehensive study, where CHK2 gene variants are analyzed using in silico tools hence it will be of great help while considering large scale studies and also in developing precision medicines related to these polymorphisms in the era of personalized medicine.

show abstract

“…CYP , CHEK2 and MTHFR were also studied and their involvement in BC showed that they may modify susceptibility to BC [ 70 , 96 , 97 ]. TNF-alpha, Enos , RAD50, CCND1, NBS1 and SULT1A1 genes were studied in Asia and the results exclude the possible role of RAD50 and NBS1 in familial BC [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Genetics of breast cancer in African populations: a literature review

Abbad

Baba

Dehbi

et al. 2018

Glob. Health Epidemiol.

View full text Add to dashboard Cite

Breast cancer (BC) is one of the most complex, diverse and leading cause of death in women worldwide. The present investigation aims to explore genes panel associated with BC in different African regions, and compare them to those studied worldwide.We extracted relevant information from 43 studies performed in Africa using the following criteria: case-control study, association between genetic variations and BC risk. Data were provided on mutations and polymorphisms associated with BC without fixing a specific date. Case-only studies and clinical trials were excluded.Our study revealed that the majority of African BC genetic studies remain restricted to the investigation of BRCA1 and BRCA2 genes and differences in their mutations spectrum. Therefore, it is necessary to encourage African researchers to characterize more genes involved in BC using methods generating global information such as next-generation sequencing in order to guide specific and more effective therapeutic strategies for the African community.

show abstract

Novel Nonsense Variants c.58C>T (p.Q20X) and c.256G>T (p.E85X) in the CHEK2 Gene Identified dentified in Breast Cancer Patients from Balochistan

Cited by 5 publications

References 37 publications

Current perspectives on CHEK2 mutations in breast cancer

Current perspectives on CHEK2 mutations in breast cancer

Computational analysis of high-risk SNPs in human CHK2 gene responsible for hereditary breast cancer: A functional and structural impact

Genetics of breast cancer in African populations: a literature review

Contact Info

Product

Resources

About