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Determination of distinctive hypomethylated genes in African American colorectal neoplastic lesions
BACKGROUND: Few studies have analyzed progressive demethylation in the path to cancer. This is of utmost importance, especially in populations such as African Americans, who display aggressive tumors at diagnosis, and for whom markers of early neoplastic transformation are needed. Here, we determine...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273615/ https://www.ncbi.nlm.nih.gov/pubmed/32547637 http://dx.doi.org/10.1177/1756284820905482 |
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author | Ashktorab, Hassan Washington, Kareem Zarnogi, Shatha Shakoori, Afnan Varma, Sudhir Lee, Edward Shokrani, Babak Laiyemo, Adeyinka Brim, Hassan |
author_facet | Ashktorab, Hassan Washington, Kareem Zarnogi, Shatha Shakoori, Afnan Varma, Sudhir Lee, Edward Shokrani, Babak Laiyemo, Adeyinka Brim, Hassan |
author_sort | Ashktorab, Hassan |
collection | PubMed |
description | BACKGROUND: Few studies have analyzed progressive demethylation in the path to cancer. This is of utmost importance, especially in populations such as African Americans, who display aggressive tumors at diagnosis, and for whom markers of early neoplastic transformation are needed. Here, we determined hypomethylated targets in the path to colorectal cancer (CRC) using Reduced Representation Bisulfite Sequencing (RRBS). METHODS: DNA was extracted from fresh frozen tissues of patients with different colon lesions (normal, tubular adenoma, tubulovillous adenoma, and five cancers). RRBS was performed on these DNA extracts to identify hypomethylated gene targets. Alignment, mapping, and methylation analyses were performed. Pathways affected by the hypomethylated gene targets were determined using Ingenuity Pathway Analysis (IPA). RESULTS: Pairwise analyses of samples led to the identification of the following novel hypomethylated genes: ELMO3 (Engulfment and cell motility 3), SLC6A2 (Solute carrier family 6 member 2), SYNM (Synemin), and HMX2 (Homeobox 2). The ELMO3 promoter was significantly hypomethylated at five CpG sites, SYNM at two CpG sites, SLC6A2 at one CpG site, and the HMX2 gene at one CpG site. IPA placed these genes within important carcinogenic pathways. CONCLUSIONS: This work provides insight into the role of hypomethylation in colon carcinogenesis in African Americans. The identified targets affected many important pathways, as demonstrated through IPA. These targets might serve as biomarkers for early diagnosis and potential targets for therapy. |
format | Online Article Text |
id | pubmed-7273615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-72736152020-06-15 Determination of distinctive hypomethylated genes in African American colorectal neoplastic lesions Ashktorab, Hassan Washington, Kareem Zarnogi, Shatha Shakoori, Afnan Varma, Sudhir Lee, Edward Shokrani, Babak Laiyemo, Adeyinka Brim, Hassan Therap Adv Gastroenterol Original Research BACKGROUND: Few studies have analyzed progressive demethylation in the path to cancer. This is of utmost importance, especially in populations such as African Americans, who display aggressive tumors at diagnosis, and for whom markers of early neoplastic transformation are needed. Here, we determined hypomethylated targets in the path to colorectal cancer (CRC) using Reduced Representation Bisulfite Sequencing (RRBS). METHODS: DNA was extracted from fresh frozen tissues of patients with different colon lesions (normal, tubular adenoma, tubulovillous adenoma, and five cancers). RRBS was performed on these DNA extracts to identify hypomethylated gene targets. Alignment, mapping, and methylation analyses were performed. Pathways affected by the hypomethylated gene targets were determined using Ingenuity Pathway Analysis (IPA). RESULTS: Pairwise analyses of samples led to the identification of the following novel hypomethylated genes: ELMO3 (Engulfment and cell motility 3), SLC6A2 (Solute carrier family 6 member 2), SYNM (Synemin), and HMX2 (Homeobox 2). The ELMO3 promoter was significantly hypomethylated at five CpG sites, SYNM at two CpG sites, SLC6A2 at one CpG site, and the HMX2 gene at one CpG site. IPA placed these genes within important carcinogenic pathways. CONCLUSIONS: This work provides insight into the role of hypomethylation in colon carcinogenesis in African Americans. The identified targets affected many important pathways, as demonstrated through IPA. These targets might serve as biomarkers for early diagnosis and potential targets for therapy. SAGE Publications 2020-05-27 /pmc/articles/PMC7273615/ /pubmed/32547637 http://dx.doi.org/10.1177/1756284820905482 Text en © The Author(s), 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Ashktorab, Hassan Washington, Kareem Zarnogi, Shatha Shakoori, Afnan Varma, Sudhir Lee, Edward Shokrani, Babak Laiyemo, Adeyinka Brim, Hassan Determination of distinctive hypomethylated genes in African American colorectal neoplastic lesions |
title | Determination of distinctive hypomethylated genes in African American
colorectal neoplastic lesions |
title_full | Determination of distinctive hypomethylated genes in African American
colorectal neoplastic lesions |
title_fullStr | Determination of distinctive hypomethylated genes in African American
colorectal neoplastic lesions |
title_full_unstemmed | Determination of distinctive hypomethylated genes in African American
colorectal neoplastic lesions |
title_short | Determination of distinctive hypomethylated genes in African American
colorectal neoplastic lesions |
title_sort | determination of distinctive hypomethylated genes in african american
colorectal neoplastic lesions |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273615/ https://www.ncbi.nlm.nih.gov/pubmed/32547637 http://dx.doi.org/10.1177/1756284820905482 |
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