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Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients

In addition to classic germline APC gene variants, APC mosaicism and deep intronic germline APC variants have also been reported to be causes of adenomatous polyposis. In this study, we investigated 80 unexplained colorectal polyposis patients without germline pathogenic variants in known polyposis...

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Autores principales: Elsayed, Fadwa A., Tops, Carli M. J., Nielsen, Maartje, Morreau, Hans, Hes, Frederik J., van Wezel, Tom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799582/
https://www.ncbi.nlm.nih.gov/pubmed/33683519
http://dx.doi.org/10.1007/s10689-021-00236-2
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author Elsayed, Fadwa A.
Tops, Carli M. J.
Nielsen, Maartje
Morreau, Hans
Hes, Frederik J.
van Wezel, Tom
author_facet Elsayed, Fadwa A.
Tops, Carli M. J.
Nielsen, Maartje
Morreau, Hans
Hes, Frederik J.
van Wezel, Tom
author_sort Elsayed, Fadwa A.
collection PubMed
description In addition to classic germline APC gene variants, APC mosaicism and deep intronic germline APC variants have also been reported to be causes of adenomatous polyposis. In this study, we investigated 80 unexplained colorectal polyposis patients without germline pathogenic variants in known polyposis predisposing genes to detect mosaic and deep intronic APC variants. All patients developed more than 50 colorectal polyps, with adenomas being predominantly observed. To detect APC mosaicism, we performed next-generation sequencing (NGS) in leukocyte DNA. Furthermore, using Sanger sequencing, the cohort was screened for the following previously reported deep intronic pathogenic germline APC variants: c.1408 + 731C > T, p.(Gly471Serfs*55), c.1408 + 735A > T, p.(Gly471Serfs*55), c.1408 + 729A > G, p.(Gly471Serfs*55) and c.532-941G > A, p.(Phe178Argfs*22). We did not detect mosaic or intronic APC variants in the screened unexplained colorectal polyposis patients. The results of this study indicate that the deep intronic APC variants investigated in this study are not a cause of colorectal polyposis in this Dutch population. In addition, NGS did not detect any further mosaic variants in our cohort.
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spelling pubmed-87995822022-02-02 Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients Elsayed, Fadwa A. Tops, Carli M. J. Nielsen, Maartje Morreau, Hans Hes, Frederik J. van Wezel, Tom Fam Cancer Original Article In addition to classic germline APC gene variants, APC mosaicism and deep intronic germline APC variants have also been reported to be causes of adenomatous polyposis. In this study, we investigated 80 unexplained colorectal polyposis patients without germline pathogenic variants in known polyposis predisposing genes to detect mosaic and deep intronic APC variants. All patients developed more than 50 colorectal polyps, with adenomas being predominantly observed. To detect APC mosaicism, we performed next-generation sequencing (NGS) in leukocyte DNA. Furthermore, using Sanger sequencing, the cohort was screened for the following previously reported deep intronic pathogenic germline APC variants: c.1408 + 731C > T, p.(Gly471Serfs*55), c.1408 + 735A > T, p.(Gly471Serfs*55), c.1408 + 729A > G, p.(Gly471Serfs*55) and c.532-941G > A, p.(Phe178Argfs*22). We did not detect mosaic or intronic APC variants in the screened unexplained colorectal polyposis patients. The results of this study indicate that the deep intronic APC variants investigated in this study are not a cause of colorectal polyposis in this Dutch population. In addition, NGS did not detect any further mosaic variants in our cohort. Springer Netherlands 2021-03-08 2022 /pmc/articles/PMC8799582/ /pubmed/33683519 http://dx.doi.org/10.1007/s10689-021-00236-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Elsayed, Fadwa A.
Tops, Carli M. J.
Nielsen, Maartje
Morreau, Hans
Hes, Frederik J.
van Wezel, Tom
Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients
title Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients
title_full Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients
title_fullStr Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients
title_full_unstemmed Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients
title_short Use of sanger and next-generation sequencing to screen for mosaic and intronic APC variants in unexplained colorectal polyposis patients
title_sort use of sanger and next-generation sequencing to screen for mosaic and intronic apc variants in unexplained colorectal polyposis patients
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8799582/
https://www.ncbi.nlm.nih.gov/pubmed/33683519
http://dx.doi.org/10.1007/s10689-021-00236-2
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