Assessment of<i>TP53</i>Polymorphisms and<i>MDM2</i>SNP309 in Premenopausal Breast Cancer Risk

Samuel, Nardin; Said, Badr Id; Guha, Tanya; Novokmet, Ana; Li, Weili; Silwal-Pandit, Laxmi; Børrsen-Dale, Anne-Lise; Langerød, Anita; Hudson, Thomas J.; Malkin, David

doi:10.1002/humu.23154

Cited by 7 publications

(6 citation statements)

References 25 publications

(27 reference statements)

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“…For example, loss of function due to mutations in tumour suppressor genes (like TP53 [Tumour protein p53]), can lead to cancer and its progression. Replacement of mutated genes with the functional version of TP53 can inhibit the growth of breast cancer tumours and induce apoptosis 61,88 …”

Section: Gene Therapy Strategies For Bc Treatmentmentioning

confidence: 99%

Gene therapy: A promising approach for breast cancer treatment

Dastjerd

Valibeik

Monfared

et al. 2021

Cell Biochemistry & Function

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Breast cancer (BC) is the most prevalent malignancy and the second leading cause of death among women worldwide that is caused by numerous genetic and environmental factors. Hence, effective treatment for this type of cancer requires new therapeutic approaches. The traditional methods for treating this cancer have side effects, therefore so much research have been performed in last decade to find new methods to alleviate these problems. The study of the molecular basis of breast cancer has led to the introduction of gene therapy as an effective therapeutic approach for this cancer. Gene therapy involves sending genetic material through a vector into target cells, which is followed by a correction, addition, or suppression of the gene. In this technique, it is necessary to target tumour cells without affecting normal cells. In addition, clinical trial studies have shown that this approach is less toxic than traditional therapies. This study will review various aspects of breast cancer, gene therapy strategies, limitations, challenges and recent studies in this area.

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Section: Gene Therapy Strategies For Bc Treatmentmentioning

confidence: 99%

Gene therapy: A promising approach for breast cancer treatment

Dastjerd

Valibeik

Monfared

et al. 2021

Cell Biochemistry & Function

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“…The connections between coilin and cancer have not been systematically assessed. In recent years, the associations of SNPs and disease risks have been demonstrated in many studies [22][23][24]. Here, we performed clinical bioinformatic analysis and found that coilin mutation at residue 121 or 145 is rare in patients of various cancer types.…”

Section: Discussionmentioning

confidence: 86%

“…In recent years, large-scale sequencing projects to determine the SNPs of various human populations throughout the globe have been carried out [ 19 , 20 , 21 ]. Evidence has shown that SNP is one of the potential factors that determine the risk of hundreds of diseases, including cancers [ 22 , 23 , 24 ]. Among the SNP types, the nonsynonymous (missense) SNPs have the highest probability of affecting protein functions, changing cell phenotypes, and resulting in diseases [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

The Impact of Coilin Nonsynonymous SNP Variants E121K and V145I on Cell Growth and Cajal Body Formation: The First Characterization

Yao

Tan

Liang

et al. 2020

Genes

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Coilin is the main component of Cajal body (CB), a membraneless organelle that is involved in the biogenesis of ribonucleoproteins and telomerase, cell cycle, and cell growth. The disruption of CBs is linked to neurodegenerative diseases and potentially cancers. The coilin gene (COIL) contains two nonsynonymous SNPs: rs116022828 (E121K) and rs61731978 (V145I). Here, we investigated for the first time the functional impacts of these coilin SNPs on CB formation, coilin subcellular localization, microtubule formation, cell growth, and coilin expression and protein structure. We revealed that both E121K and V145I mutants could disrupt CB formation and result in various patterns of subcellular localization with survival motor neuron protein. Noteworthy, many of the E121K cells showed nucleolar coilin accumulation. The microtubule regrowth and cell cycle assays indicated that the E121K cells appeared to be trapped in the S and G2/M phases of cell cycle, resulting in reduced cell proliferation. In silico protein structure prediction suggested that the E121K mutation caused greater destabilization on the coilin structure than the V145I mutation. Additionally, clinical bioinformatic analysis indicated that coilin expression levels could be a risk factor for cancer, depending on the cancer types and races.

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“…Specifically, she was diagnosed at the very young age of 32 with HER2-enriched breast cancer and had a first-degree family history, with a mother affected by uterine sarcoma and a father by hepatocellular carcinoma. However, other studies focusing on the premenopausal population underline that early-onset breast cancer cannot be attributed to TP53 polymorphisms alone, although specific mutations occur in this young cohort in higher frequency, without, however, always affecting p53 transactivation function [ 45 ]. Concerning CHEK2 , we identified by a targeted gene sequencing panel three premenopausal patients who carried germline pathogenic mutations that affect the expression of this key cell cycle checkpoint kinase.…”

Section: Discussionmentioning

confidence: 99%

Multi-Gene Mutation Profiling by Targeted Next-Generation Sequencing in Premenopausal Breast Cancer

Zografos

Andrikopoulou

Papatheodoridi

et al. 2022

Genes

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Breast cancer has distinct etiology, prognoses, and clinical outcomes at premenopausal ages. Determination of the frequency of germline and somatic mutations will refine our understanding of the genetic contribution to premenopausal breast cancer susceptibility. We applied a comprehensive next generation sequencing-based approach to analyze blood and/or tissue samples of 54 premenopausal breast cancer patients treated in our clinic. Genetic testing results were descriptively analyzed in correlation with clinicopathological data. In the present study, 42.5% of premenopausal breast cancer patients tested carried pathogenic mutations in cancer predisposition genes (CHEK2, BRCA1, TP53, and MUTYH). Germline variants of unknown/uncertain significance (VUSs) in eight different cancer susceptibility genes, namely BRCA1, BRCA2, CHEK2, RAD51C, RAD51D, ATM, BRIP1, and PMS2, were also identified in 14 premenopausal patients (35%). Of the breast tumors tested, 61.8% harbored pathogenic somatic variants in tumor suppressor genes (TP53, NF1, RB), genes involved in DNA repair (BRCA1, BRCA2, ATM, RAD50), cell proliferation (PTEN, PIK3C FGFR3, AKT1, ROS1, ERBB2, NOTCH1), and cell adhesion (CTNNB1). This descriptive study employs the powerful NGS technology to highlight the high frequency of premenopausal cases attributable to genetic predisposition. Mutation identification in a larger cohort may further ensure that these patients receive tailored treatment according to their menopausal status.

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Assessment ofTP53Polymorphisms andMDM2SNP309 in Premenopausal Breast Cancer Risk

Cited by 7 publications

References 25 publications

Gene therapy: A promising approach for breast cancer treatment

Gene therapy: A promising approach for breast cancer treatment

The Impact of Coilin Nonsynonymous SNP Variants E121K and V145I on Cell Growth and Cajal Body Formation: The First Characterization

Multi-Gene Mutation Profiling by Targeted Next-Generation Sequencing in Premenopausal Breast Cancer

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