scholarly journals Exonic sequencing and MLH3 gene expression analysis of breast cancer patients

2021 ◽  
Vol 67 (3) ◽  
pp. 35-43
Author(s):  
Rozhgar A. Khailany ◽  
Mehmet Ozaslan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Exome Sequencing ◽  
Cancer Patients ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
Breast Cancer Susceptibility ◽  
Breast Cancer Patients ◽  
Cancer Susceptibility Genes ◽  
Mlh3 Gene

Breast cancer is the most common cancer in women worldwide. Detection of breast cancer susceptibility genes is an important issue. Also, MLH3 is a DNA mismatch repair gene and mutation in this gene is harmful in different cancers. This study aimed to use exome sequencing to uncover previously undetected breast cancer-predisposing variants. Also, we investigated the MLH3 gene expression of breast cancer patients which can be a breast cancer susceptibility gene. A total of 80 samples including 40 paired normal and cancer tissue samples were collected at Zheen International Hospital, Erbil, Iraq. Exome sequencing was used to identify mutations. Different in silico tools were used to predict the effect of mutation on the structural features or protein function. Real-time PCR was used for assessing the expression of MLH3 in breast cancer patients. We identified 26 variants in breast cancer patients, 22 inherited variants were found in MLH3, CHECK2, BRCA1, BRCA2, BLM, TP53, MSH6, NBN and PTEN genes and 4 somatic variants were found in PALB2, RAD50 and RBM10 genes. It was found that the expression of the MLH3 gene in tumor samples was significantly down-regulated compared with normal tissues. Statistically, high significance was found. The decreased expression of MLH3 was significant in all ranges of ages and all breast cancer types. Also, the expression of MLH3 decreased significantly in patients with breast cancer grades of II and III. In conclusion, MLH3 can be used as a susceptibility gene especially in grades II and III of breast cancer.

scholarly journals Under-ascertainment of breast cancer susceptibility gene carriers in a cohort of New Zealand female breast cancer patients

2020 ◽  
Author(s):  
Vanessa Lattimore ◽  
Michael T. Parsons ◽  
Amanda B. Spurdle ◽  
John Pearson ◽  
Klaus Lehnert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
New Zealand ◽  
High Risk ◽  
Cancer Patients ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
Breast Cancer Susceptibility ◽  
Pathogenic Variant ◽  
Breast Cancer Susceptibility Gene ◽  
Breast Cancer Patients

Abstract Background Diagnostic screening for pathogenic variants in breast cancer susceptibility genes, including BRCA1, BRCA2, PALB2, PTEN and TP53, may be offered to New Zealanders from suspected high-risk breast (and ovarian) cancer families. However, it is unknown how many high-risk pathogenic variant carriers in New Zealand are not offered genetic screening using existing triage tools and guidelines for breast (and ovarian) cancer patients. Methods Panel-gene sequencing of the coding and non-coding regions of the BRCA1 and BRCA2 genes, and the coding regions and splice sites of CDH1, PALB2, PTEN and TP53, was undertaken for an unselected cohort of 367 female breast cancer patients. A total of 1685 variants were evaluated using the ENIGMA and the ACMG/AMP variant classification guidelines. Results Our study identified that 13 (3.5%) breast cancer patients carried a pathogenic or likely pathogenic variant in BRCA1, BRCA2, PALB2, or PTEN. A significantly higher number of pathogenic variant carriers had grade 3 tumours (10/13) when compared to non-carriers; however, no other clinicopathological characteristics were found to be significantly different between (likely) pathogenic variant carriers and non-carriers, nor between variant of unknown significance carriers and non-carriers. Notably, 46% of the identified (likely) pathogenic variant carriers had not been referred for a genetic assessment and consideration of genetic testing. Conclusion Our study shows a potential under-ascertainment of women carrying a (likely) pathogenic variant in a high-risk breast cancer susceptibility gene. These results suggest that further research into testing pathways for New Zealand breast cancer patients may be required to reduce the impact of hereditary cancer syndromes for these individuals and their families.

scholarly journals Germline breast cancer susceptibility genes, tumor characteristics, and survival

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Peh Joo Ho ◽  
Alexis J. Khng ◽  
Hui Wen Loh ◽  
Weang-Kee Ho ◽  
Cheng Har Yip ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Tumor Characteristics ◽  
Breast Cancer Patients ◽  
Luminal B ◽  
Cancer Susceptibility Genes

Abstract Background Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent. Methods Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease. Results PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35–5.17], moderately vs well-differentiated 2.33 [1.56–3.49]), as well as luminal B [HER−] and triple-negative subtypes (vs luminal A 2.15 [1.58–2.92] and 2.85 [2.17–3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2−] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16–2.28]). Conclusions PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.

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