Mutation Profiling of Premalignant Colorectal Neoplasia
Accumulation of allelic variants in genes that regulate cellular proliferation, differentiation, and apoptosis may result in expansion of the aberrant intestinal epithelium, generating adenomas. Herein, we compared the mutation profiles of conventional colorectal adenomas (CNADs) across stages of pr...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Gastroenterology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2019/2542640 |
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| author | Jakub Karczmarski Krzysztof Goryca Jacek Pachlewski Michalina Dabrowska Kazimiera Pysniak Agnieszka Paziewska Maria Kulecka Malgorzata Lenarcik Andrzej Mroz Michal Mikula Jerzy Ostrowski |
| author_facet | Jakub Karczmarski Krzysztof Goryca Jacek Pachlewski Michalina Dabrowska Kazimiera Pysniak Agnieszka Paziewska Maria Kulecka Malgorzata Lenarcik Andrzej Mroz Michal Mikula Jerzy Ostrowski |
| author_sort | Jakub Karczmarski |
| collection | DOAJ |
| description | Accumulation of allelic variants in genes that regulate cellular proliferation, differentiation, and apoptosis may result in expansion of the aberrant intestinal epithelium, generating adenomas. Herein, we compared the mutation profiles of conventional colorectal adenomas (CNADs) across stages of progression towards early carcinoma. DNA was isolated from 17 invasive adenocarcinomas (ACs) and 58 large CNADs, including 19 with low-grade dysplasia (LGD), 21 with LGD adjacent to areas of high-grade dysplasia and/or carcinoma (LGD-H), and 28 with high-grade dysplasia (HGD). Ion AmpliSeq Comprehensive Cancer Panel libraries were prepared and sequenced on the Ion Proton. We identified 956 unique allelic variants; of these, 499 were considered nonsynonymous variants. Eleven genes (APC, KRAS, SYNE1, NOTCH4, BLNK, FBXW7, GNAS, KMT2D, TAF1L, TCF7L2, and TP53) were mutated in at least 15% of all samples. Out of frequently mutated genes, TP53 and BCL2 had a consistent trend in mutation prevalence towards malignancy, while two other genes (HNF1A and FBXW7) exhibited the opposite trend. HGD adenomas had significantly higher mutation rates than LGD adenomas, while LGD-H adenomas exhibited mutation frequencies similar to those of LGD adenomas. A significant increase in copy number variant frequency was observed from LGD through HGD to malignant samples. The profiling of advanced CNADs demonstrated variations in mutation patterns among colorectal premalignancies. Only limited numbers of genes were repeatedly mutated while the majority were altered in single cases. Most genetic alterations in adenomas can be considered early contributors to colorectal carcinogenesis. |
| format | Article |
| id | doaj-art-0f8ccbd591ba4022a89ae4068b2296ab |
| institution | Kabale University |
| issn | 1687-6121 1687-630X |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Gastroenterology Research and Practice |
| spelling | doaj-art-0f8ccbd591ba4022a89ae4068b2296ab2025-08-20T03:54:28ZengWileyGastroenterology Research and Practice1687-61211687-630X2019-01-01201910.1155/2019/25426402542640Mutation Profiling of Premalignant Colorectal NeoplasiaJakub Karczmarski0Krzysztof Goryca1Jacek Pachlewski2Michalina Dabrowska3Kazimiera Pysniak4Agnieszka Paziewska5Maria Kulecka6Malgorzata Lenarcik7Andrzej Mroz8Michal Mikula9Jerzy Ostrowski10Department of Genetics, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, PolandDepartment of Genetics, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, PolandDepartment of Gastroenterology, Hepatology and Clinical Oncology, Center for Postgraduate Medical Education, 01-813 Warsaw, PolandDepartment of Genetics, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, PolandDepartment of Genetics, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, PolandDepartment of Gastroenterology, Hepatology and Clinical Oncology, Center for Postgraduate Medical Education, 01-813 Warsaw, PolandDepartment of Gastroenterology, Hepatology and Clinical Oncology, Center for Postgraduate Medical Education, 01-813 Warsaw, PolandDepartment of Gastroenterology, Hepatology and Clinical Oncology, Center for Postgraduate Medical Education, 01-813 Warsaw, PolandDepartment of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, PolandDepartment of Genetics, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, PolandDepartment of Genetics, Maria Sklodowska-Curie Institute-Oncology Center, 02-781 Warsaw, PolandAccumulation of allelic variants in genes that regulate cellular proliferation, differentiation, and apoptosis may result in expansion of the aberrant intestinal epithelium, generating adenomas. Herein, we compared the mutation profiles of conventional colorectal adenomas (CNADs) across stages of progression towards early carcinoma. DNA was isolated from 17 invasive adenocarcinomas (ACs) and 58 large CNADs, including 19 with low-grade dysplasia (LGD), 21 with LGD adjacent to areas of high-grade dysplasia and/or carcinoma (LGD-H), and 28 with high-grade dysplasia (HGD). Ion AmpliSeq Comprehensive Cancer Panel libraries were prepared and sequenced on the Ion Proton. We identified 956 unique allelic variants; of these, 499 were considered nonsynonymous variants. Eleven genes (APC, KRAS, SYNE1, NOTCH4, BLNK, FBXW7, GNAS, KMT2D, TAF1L, TCF7L2, and TP53) were mutated in at least 15% of all samples. Out of frequently mutated genes, TP53 and BCL2 had a consistent trend in mutation prevalence towards malignancy, while two other genes (HNF1A and FBXW7) exhibited the opposite trend. HGD adenomas had significantly higher mutation rates than LGD adenomas, while LGD-H adenomas exhibited mutation frequencies similar to those of LGD adenomas. A significant increase in copy number variant frequency was observed from LGD through HGD to malignant samples. The profiling of advanced CNADs demonstrated variations in mutation patterns among colorectal premalignancies. Only limited numbers of genes were repeatedly mutated while the majority were altered in single cases. Most genetic alterations in adenomas can be considered early contributors to colorectal carcinogenesis.http://dx.doi.org/10.1155/2019/2542640 |
| spellingShingle | Jakub Karczmarski Krzysztof Goryca Jacek Pachlewski Michalina Dabrowska Kazimiera Pysniak Agnieszka Paziewska Maria Kulecka Malgorzata Lenarcik Andrzej Mroz Michal Mikula Jerzy Ostrowski Mutation Profiling of Premalignant Colorectal Neoplasia Gastroenterology Research and Practice |
| title | Mutation Profiling of Premalignant Colorectal Neoplasia |
| title_full | Mutation Profiling of Premalignant Colorectal Neoplasia |
| title_fullStr | Mutation Profiling of Premalignant Colorectal Neoplasia |
| title_full_unstemmed | Mutation Profiling of Premalignant Colorectal Neoplasia |
| title_short | Mutation Profiling of Premalignant Colorectal Neoplasia |
| title_sort | mutation profiling of premalignant colorectal neoplasia |
| url | http://dx.doi.org/10.1155/2019/2542640 |
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