Novel Genetic Markers for Early Detection of Elevated Breast Cancer Risk in Women
This study suggests that two newly discovered variants in the <i>MSH2</i> gene, which codes for a DNA mismatch repair (MMR) protein, can be associated with a high risk of breast cancer. While variants in the MSH2 gene are known to be linked with an elevated cancer risk, the MSH2 gene is...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-09-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/20/19/4828 |
id |
doaj-3b380798b0384e0e9b14658fe6b5c312 |
---|---|
record_format |
Article |
spelling |
doaj-3b380798b0384e0e9b14658fe6b5c3122020-11-24T22:10:06ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-09-012019482810.3390/ijms20194828ijms20194828Novel Genetic Markers for Early Detection of Elevated Breast Cancer Risk in WomenBohua Wu0Yunhui Peng1Julia Eggert2Emil Alexov3Healthcare Genetics, School of Nursing, Clemson University, Clemson, SC 29634, USAComputational Biophysics and Bioinformatics, Department of Physics, Clemson University, Clemson, SC 29634, USAHealthcare Genetics, School of Nursing, Clemson University, Clemson, SC 29634, USAHealthcare Genetics, School of Nursing, Clemson University, Clemson, SC 29634, USAThis study suggests that two newly discovered variants in the <i>MSH2</i> gene, which codes for a DNA mismatch repair (MMR) protein, can be associated with a high risk of breast cancer. While variants in the MSH2 gene are known to be linked with an elevated cancer risk, the MSH2 gene is not a part of the standard kit for testing patients for elevated breast cancer risk. Here we used the results of genetic testing of women diagnosed with breast cancer, but who did not have variants in <i>BRCA1</i> and <i>BRCA2</i> genes. Instead, the test identified four variants with unknown significance (VUS) in the <i>MSH2</i> gene. Here, we carried in silico analysis to develop a classifier that can distinguish pathogenic from benign mutations in <i>MSH2</i> genes taken from ClinVar. The classifier was then used to classify VUS in <i>MSH2</i> genes, and two of them, p.Ala272Val and p.Met592Val, were predicted to be pathogenic mutations. These two mutations were found in women with breast cancer who did not have mutations in <i>BRCA1</i> and <i>BRCA2</i> genes, and thus they are suggested to be considered as new bio-markers for the early detection of elevated breast cancer risk. However, before this is done, an in vitro validation of mutation pathogenicity is needed and, moreover, the presence of these mutations should be demonstrated in a higher number of patients or in families with breast cancer history.https://www.mdpi.com/1422-0067/20/19/4828msh2breast cancerpersonalized medicineearly diagnosticscomputational modelingdisease-causing mutationsvariants |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bohua Wu Yunhui Peng Julia Eggert Emil Alexov |
spellingShingle |
Bohua Wu Yunhui Peng Julia Eggert Emil Alexov Novel Genetic Markers for Early Detection of Elevated Breast Cancer Risk in Women International Journal of Molecular Sciences msh2 breast cancer personalized medicine early diagnostics computational modeling disease-causing mutations variants |
author_facet |
Bohua Wu Yunhui Peng Julia Eggert Emil Alexov |
author_sort |
Bohua Wu |
title |
Novel Genetic Markers for Early Detection of Elevated Breast Cancer Risk in Women |
title_short |
Novel Genetic Markers for Early Detection of Elevated Breast Cancer Risk in Women |
title_full |
Novel Genetic Markers for Early Detection of Elevated Breast Cancer Risk in Women |
title_fullStr |
Novel Genetic Markers for Early Detection of Elevated Breast Cancer Risk in Women |
title_full_unstemmed |
Novel Genetic Markers for Early Detection of Elevated Breast Cancer Risk in Women |
title_sort |
novel genetic markers for early detection of elevated breast cancer risk in women |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-09-01 |
description |
This study suggests that two newly discovered variants in the <i>MSH2</i> gene, which codes for a DNA mismatch repair (MMR) protein, can be associated with a high risk of breast cancer. While variants in the MSH2 gene are known to be linked with an elevated cancer risk, the MSH2 gene is not a part of the standard kit for testing patients for elevated breast cancer risk. Here we used the results of genetic testing of women diagnosed with breast cancer, but who did not have variants in <i>BRCA1</i> and <i>BRCA2</i> genes. Instead, the test identified four variants with unknown significance (VUS) in the <i>MSH2</i> gene. Here, we carried in silico analysis to develop a classifier that can distinguish pathogenic from benign mutations in <i>MSH2</i> genes taken from ClinVar. The classifier was then used to classify VUS in <i>MSH2</i> genes, and two of them, p.Ala272Val and p.Met592Val, were predicted to be pathogenic mutations. These two mutations were found in women with breast cancer who did not have mutations in <i>BRCA1</i> and <i>BRCA2</i> genes, and thus they are suggested to be considered as new bio-markers for the early detection of elevated breast cancer risk. However, before this is done, an in vitro validation of mutation pathogenicity is needed and, moreover, the presence of these mutations should be demonstrated in a higher number of patients or in families with breast cancer history. |
topic |
msh2 breast cancer personalized medicine early diagnostics computational modeling disease-causing mutations variants |
url |
https://www.mdpi.com/1422-0067/20/19/4828 |
work_keys_str_mv |
AT bohuawu novelgeneticmarkersforearlydetectionofelevatedbreastcancerriskinwomen AT yunhuipeng novelgeneticmarkersforearlydetectionofelevatedbreastcancerriskinwomen AT juliaeggert novelgeneticmarkersforearlydetectionofelevatedbreastcancerriskinwomen AT emilalexov novelgeneticmarkersforearlydetectionofelevatedbreastcancerriskinwomen |
_version_ |
1725809330022776832 |