DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis.
The contribution of DNA methylation to the metastatic process in colorectal cancers (CRCs) is unclear.We evaluated the methylation status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13, THBS1, MGMT, HPP1 and ERα) by bisulfite-pyrosequencing in 79 CRCs comprising 36 CRCs withou...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3221680?pdf=render |
| _version_ | 1828264084572733440 |
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| author | Kazuo Konishi Yoshiyuki Watanabe Lanlan Shen Yi Guo Ryan J Castoro Kimie Kondo Woonbok Chung Saira Ahmed Jaroslav Jelinek Yanis A Boumber Marcos R Estecio Shinji Maegawa Yutaka Kondo Fumio Itoh Michio Imawari Stanley R Hamilton Jean-Pierre J Issa |
| author_facet | Kazuo Konishi Yoshiyuki Watanabe Lanlan Shen Yi Guo Ryan J Castoro Kimie Kondo Woonbok Chung Saira Ahmed Jaroslav Jelinek Yanis A Boumber Marcos R Estecio Shinji Maegawa Yutaka Kondo Fumio Itoh Michio Imawari Stanley R Hamilton Jean-Pierre J Issa |
| author_sort | Kazuo Konishi |
| collection | DOAJ |
| description | The contribution of DNA methylation to the metastatic process in colorectal cancers (CRCs) is unclear.We evaluated the methylation status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13, THBS1, MGMT, HPP1 and ERα) by bisulfite-pyrosequencing in 79 CRCs comprising 36 CRCs without liver metastasis and 43 CRCs with liver metastasis, including 16 paired primary CRCs and liver metastasis. We also performed methylated CpG island amplification microarrays (MCAM) in three paired primary and metastatic cancers.Methylation of p14, TIMP3 and HPP1 in primary CRCs progressively decreased from absence to presence of liver metastasis (13.1% vs. 4.3%; 14.8% vs. 3.7%; 43.9% vs. 35.8%, respectively) (P<.05). When paired primary and metastatic tumors were compared, only MGMT methylation was significantly higher in metastatic cancers (27.4% vs. 13.4%, P = .013), and this difference was due to an increase in methylation density rather than frequency in the majority of cases. MCAM showed an average 7.4% increase in DNA methylated genes in the metastatic samples. The numbers of differentially hypermethylated genes in the liver metastases increased with increasing time between resection of the primary and resection of the liver metastasis. Bisulfite-pyrosequencing validation in 12 paired samples showed that most of these increases were not conserved, and could be explained by differences in methylation density rather than frequency.Most DNA methylation differences between primary CRCs and matched liver metastasis are due to random variation and an increase in DNA methylation density rather than de-novo inactivation and silencing. Thus, DNA methylation changes occur for the most part before progression to liver metastasis. |
| first_indexed | 2024-04-13T04:19:31Z |
| format | Article |
| id | doaj.art-87da15e0342a44f18efe02cb6e7523ad |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T04:19:31Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-87da15e0342a44f18efe02cb6e7523ad2022-12-22T03:02:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2788910.1371/journal.pone.0027889DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis.Kazuo KonishiYoshiyuki WatanabeLanlan ShenYi GuoRyan J CastoroKimie KondoWoonbok ChungSaira AhmedJaroslav JelinekYanis A BoumberMarcos R EstecioShinji MaegawaYutaka KondoFumio ItohMichio ImawariStanley R HamiltonJean-Pierre J IssaThe contribution of DNA methylation to the metastatic process in colorectal cancers (CRCs) is unclear.We evaluated the methylation status of 13 genes (MINT1, MINT2, MINT31, MLH1, p16, p14, TIMP3, CDH1, CDH13, THBS1, MGMT, HPP1 and ERα) by bisulfite-pyrosequencing in 79 CRCs comprising 36 CRCs without liver metastasis and 43 CRCs with liver metastasis, including 16 paired primary CRCs and liver metastasis. We also performed methylated CpG island amplification microarrays (MCAM) in three paired primary and metastatic cancers.Methylation of p14, TIMP3 and HPP1 in primary CRCs progressively decreased from absence to presence of liver metastasis (13.1% vs. 4.3%; 14.8% vs. 3.7%; 43.9% vs. 35.8%, respectively) (P<.05). When paired primary and metastatic tumors were compared, only MGMT methylation was significantly higher in metastatic cancers (27.4% vs. 13.4%, P = .013), and this difference was due to an increase in methylation density rather than frequency in the majority of cases. MCAM showed an average 7.4% increase in DNA methylated genes in the metastatic samples. The numbers of differentially hypermethylated genes in the liver metastases increased with increasing time between resection of the primary and resection of the liver metastasis. Bisulfite-pyrosequencing validation in 12 paired samples showed that most of these increases were not conserved, and could be explained by differences in methylation density rather than frequency.Most DNA methylation differences between primary CRCs and matched liver metastasis are due to random variation and an increase in DNA methylation density rather than de-novo inactivation and silencing. Thus, DNA methylation changes occur for the most part before progression to liver metastasis.http://europepmc.org/articles/PMC3221680?pdf=render |
| spellingShingle | Kazuo Konishi Yoshiyuki Watanabe Lanlan Shen Yi Guo Ryan J Castoro Kimie Kondo Woonbok Chung Saira Ahmed Jaroslav Jelinek Yanis A Boumber Marcos R Estecio Shinji Maegawa Yutaka Kondo Fumio Itoh Michio Imawari Stanley R Hamilton Jean-Pierre J Issa DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis. PLoS ONE |
| title | DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis. |
| title_full | DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis. |
| title_fullStr | DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis. |
| title_full_unstemmed | DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis. |
| title_short | DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis. |
| title_sort | dna methylation profiles of primary colorectal carcinoma and matched liver metastasis |
| url | http://europepmc.org/articles/PMC3221680?pdf=render |
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