Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
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
_version_ 1783478508313378816
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
work_keys_str_mv AT sirajabdulk germlinepoleandpold1proofreadingdomainmutationsinendometrialcarcinomafrommiddleeasternregion
AT parvathareddysandeepkumar germlinepoleandpold1proofreadingdomainmutationsinendometrialcarcinomafrommiddleeasternregion
AT burong germlinepoleandpold1proofreadingdomainmutationsinendometrialcarcinomafrommiddleeasternregion
AT iqbalkaleem germlinepoleandpold1proofreadingdomainmutationsinendometrialcarcinomafrommiddleeasternregion
AT sirajsarah germlinepoleandpold1proofreadingdomainmutationsinendometrialcarcinomafrommiddleeasternregion
AT masooditariq germlinepoleandpold1proofreadingdomainmutationsinendometrialcarcinomafrommiddleeasternregion
AT concepcionricamicaela germlinepoleandpold1proofreadingdomainmutationsinendometrialcarcinomafrommiddleeasternregion
AT ghazwanilailaomar germlinepoleandpold1proofreadingdomainmutationsinendometrialcarcinomafrommiddleeasternregion
AT albadawiismail germlinepoleandpold1proofreadingdomainmutationsinendometrialcarcinomafrommiddleeasternregion
AT aldayelfouad germlinepoleandpold1proofreadingdomainmutationsinendometrialcarcinomafrommiddleeasternregion
AT alkurayakhawlas germlinepoleandpold1proofreadingdomainmutationsinendometrialcarcinomafrommiddleeasternregion