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Germline POLE and POLD1 proofreading domain mutations in endometrial carcinoma from Middle Eastern region
BACKGROUND: Endometrial carcinoma (EC) accounts for 5.8% of all cancers in Saudi females. Although most ECs are sporadic, 2–5% tend to be familial, being associated with Lynch syndrome and Cowden syndrome. In this study, we attempted to uncover the frequency, spectrum and phenotype of germline mutat...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907229/ https://www.ncbi.nlm.nih.gov/pubmed/31866764 http://dx.doi.org/10.1186/s12935-019-1058-9 |
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author | Siraj, Abdul K. Parvathareddy, Sandeep Kumar Bu, Rong Iqbal, Kaleem Siraj, Sarah Masoodi, Tariq Concepcion, Rica Micaela Ghazwani, Laila Omar AlBadawi, Ismail Al-Dayel, Fouad Al-Kuraya, Khawla S. |
author_facet | Siraj, Abdul K. Parvathareddy, Sandeep Kumar Bu, Rong Iqbal, Kaleem Siraj, Sarah Masoodi, Tariq Concepcion, Rica Micaela Ghazwani, Laila Omar AlBadawi, Ismail Al-Dayel, Fouad Al-Kuraya, Khawla S. |
author_sort | Siraj, Abdul K. |
collection | PubMed |
description | BACKGROUND: Endometrial carcinoma (EC) accounts for 5.8% of all cancers in Saudi females. Although most ECs are sporadic, 2–5% tend to be familial, being associated with Lynch syndrome and Cowden syndrome. In this study, we attempted to uncover the frequency, spectrum and phenotype of germline mutations in the proofreading domain of POLE and POLD1 genes in a large cohort of ECs from Middle Eastern region. METHODS: We performed Capture sequencing and Sanger sequencing to screen for proofreading domains of POLE and POLD1 genes in 432 EC cases, followed by evaluation of protein expression using immunohistochemistry. Variant interpretation was performed using PolyPhen-2, MutationAssessor, SIFT, CADD and Mutation Taster. RESULTS: In our cohort, four mutations (0.93%) were identified in 432 EC cases, two each in POLE and POLD1 proofreading domains. Furthermore, low expression of POLE and POLD1 was noted in 41.1% (170/1414) and 59.9% (251/419) of cases, respectively. Both the cases harboring POLE mutation showed high nuclear expression of POLE protein, whereas, of the two POLD1 mutant cases, one case showed high expression and another case showed low expression of POLD1 protein. CONCLUSIONS: Our study shows that germline mutations in POLE and POLD1 proofreading region are a rare cause of EC in Middle Eastern population. However, it is still feasible to screen multiple cancer related genes in EC patients from Middle Eastern region using multigene panels including POLE and POLD1. |
format | Online Article Text |
id | pubmed-6907229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69072292019-12-20 Germline POLE and POLD1 proofreading domain mutations in endometrial carcinoma from Middle Eastern region Siraj, Abdul K. Parvathareddy, Sandeep Kumar Bu, Rong Iqbal, Kaleem Siraj, Sarah Masoodi, Tariq Concepcion, Rica Micaela Ghazwani, Laila Omar AlBadawi, Ismail Al-Dayel, Fouad Al-Kuraya, Khawla S. Cancer Cell Int Primary Research BACKGROUND: Endometrial carcinoma (EC) accounts for 5.8% of all cancers in Saudi females. Although most ECs are sporadic, 2–5% tend to be familial, being associated with Lynch syndrome and Cowden syndrome. In this study, we attempted to uncover the frequency, spectrum and phenotype of germline mutations in the proofreading domain of POLE and POLD1 genes in a large cohort of ECs from Middle Eastern region. METHODS: We performed Capture sequencing and Sanger sequencing to screen for proofreading domains of POLE and POLD1 genes in 432 EC cases, followed by evaluation of protein expression using immunohistochemistry. Variant interpretation was performed using PolyPhen-2, MutationAssessor, SIFT, CADD and Mutation Taster. RESULTS: In our cohort, four mutations (0.93%) were identified in 432 EC cases, two each in POLE and POLD1 proofreading domains. Furthermore, low expression of POLE and POLD1 was noted in 41.1% (170/1414) and 59.9% (251/419) of cases, respectively. Both the cases harboring POLE mutation showed high nuclear expression of POLE protein, whereas, of the two POLD1 mutant cases, one case showed high expression and another case showed low expression of POLD1 protein. CONCLUSIONS: Our study shows that germline mutations in POLE and POLD1 proofreading region are a rare cause of EC in Middle Eastern population. However, it is still feasible to screen multiple cancer related genes in EC patients from Middle Eastern region using multigene panels including POLE and POLD1. BioMed Central 2019-12-11 /pmc/articles/PMC6907229/ /pubmed/31866764 http://dx.doi.org/10.1186/s12935-019-1058-9 Text en © The Author(s) 2019 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Siraj, Abdul K. Parvathareddy, Sandeep Kumar Bu, Rong Iqbal, Kaleem Siraj, Sarah Masoodi, Tariq Concepcion, Rica Micaela Ghazwani, Laila Omar AlBadawi, Ismail Al-Dayel, Fouad Al-Kuraya, Khawla S. Germline POLE and POLD1 proofreading domain mutations in endometrial carcinoma from Middle Eastern region |
title | Germline POLE and POLD1 proofreading domain mutations in endometrial carcinoma from Middle Eastern region |
title_full | Germline POLE and POLD1 proofreading domain mutations in endometrial carcinoma from Middle Eastern region |
title_fullStr | Germline POLE and POLD1 proofreading domain mutations in endometrial carcinoma from Middle Eastern region |
title_full_unstemmed | Germline POLE and POLD1 proofreading domain mutations in endometrial carcinoma from Middle Eastern region |
title_short | Germline POLE and POLD1 proofreading domain mutations in endometrial carcinoma from Middle Eastern region |
title_sort | germline pole and pold1 proofreading domain mutations in endometrial carcinoma from middle eastern region |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907229/ https://www.ncbi.nlm.nih.gov/pubmed/31866764 http://dx.doi.org/10.1186/s12935-019-1058-9 |
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