Reviewer's report
Title:The overmethylated genes in Helicobacter pylori-infected gastric mucosa
are demethylated in gastric cancers
Version: 1Date:22 July 2010
Reviewer: Hiromu Suzuki
Reviewer's report:
In this manuscript, Hong et al. demonstrated that methylation of transitional CpG
sites are influenced by (1) distance from retroelements, (2) lack or presence of
CpG island, (3) H. pylori infection in non-cancerous gastric mucosa and (4) LOH
status in cancer. These findings are quite interesting and important, although the
first and second points are already described in their previous reports. However,
there are several concerns as listed below, which requires revision of this
manuscript before acceptance.
Major Compulsory Revisions
1. Does methylation in the transitional CpG sites correlate with gene expression
in the specimens used in this study? Only the SAGE tag results in normal
stomach is shown, and this point is not mentioned.
2. Is there any correlation between the transitional CpG sites methylation and
neighboring CpG island methylation? It is of interest to see whether CpG islands
are methylated or not, when the neighboring transitional CpG sites are
methylated by H. pylori infection.
3. Page 18: Are there any functional evidence for the statement "In cancer tissue
that undergoes the LOH event that reduces a gene dose, the remaining gene
copies have the increased possibility of using the nuclear proteins and this would
lead to the demethylation of transitional-CpG segments"? If so, please include a
citation for this statement. If not, please show functional evidence that
hypomethylation is a consequence of LOH in cancer.
4. Page 21: "This study suggests that the concurrent methylation of multiple
CpGisland genes initiates and sustains the adaptive differentiation of newly fixed
stem cells in the gastric mucosa infected with H. pylori, and that the LOH-induced
DNA demethylation and discordant methylation of stomach-specific genes may
facilitate gastric carcinogenesis by reactivating a stem-cell intrinsic program."
This study does not provide enough functional evidences to draw this conclusion.
Minor Essential Revisions
5. "Overmethylation" and "Undermethylation" are not commonly used terms to
describe DNA methylation, and the authors have used "hypermethylation" and
"hypomethylation" in their previous manuscript (Kim YH et al. BMC Cancer,
2006). Is there any specific reason to use these uncommon terms in this
manuscript?
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:The overmethylated genes in Helicobacter pylori-infected gastric mucosa
are demethylated in gastric cancers
Version: 1Date:22 July 2010
Reviewer: Hiromu Suzuki
Reviewer's report:
In this manuscript, Hong et al. demonstrated that methylation of transitional CpG
sites are influenced by (1) distance from retroelements, (2) lack or presence of
CpG island, (3) H. pylori infection in non-cancerous gastric mucosa and (4) LOH
status in cancer. These findings are quite interesting and important, although the
first and second points are already described in their previous reports. However,
there are several concerns as listed below, which requires revision of this
manuscript before acceptance.
Major Compulsory Revisions
1. Does methylation in the transitional CpG sites correlate with gene expression
in the specimens used in this study? Only the SAGE tag results in normal
stomach is shown, and this point is not mentioned.
2. Is there any correlation between the transitional CpG sites methylation and
neighboring CpG island methylation? It is of interest to see whether CpG islands
are methylated or not, when the neighboring transitional CpG sites are
methylated by H. pylori infection.
3. Page 18: Are there any functional evidence for the statement "In cancer tissue
that undergoes the LOH event that reduces a gene dose, the remaining gene
copies have the increased possibility of using the nuclear proteins and this would
lead to the demethylation of transitional-CpG segments"? If so, please include a
citation for this statement. If not, please show functional evidence that
hypomethylation is a consequence of LOH in cancer.
4. Page 21: "This study suggests that the concurrent methylation of multiple
CpGisland genes initiates and sustains the adaptive differentiation of newly fixed
stem cells in the gastric mucosa infected with H. pylori, and that the LOH-induced
DNA demethylation and discordant methylation of stomach-specific genes may
facilitate gastric carcinogenesis by reactivating a stem-cell intrinsic program."
This study does not provide enough functional evidences to draw this conclusion.
Minor Essential Revisions
5. "Overmethylation" and "Undermethylation" are not commonly used terms to
describe DNA methylation, and the authors have used "hypermethylation" and
"hypomethylation" in their previous manuscript (Kim YH et al. BMC Cancer,
2006). Is there any specific reason to use these uncommon terms in this
manuscript?
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:The overmethylated genes in Helicobacter pylori-infected gastric mucosa
are demethylated in gastric cancers
Version: 1Date:22 July 2010
Reviewer: Hiromu Suzuki
Reviewer's report:
In this manuscript, Hong et al. demonstrated that methylation of transitional CpG
sites are influenced by (1) distance from retroelements, (2) lack or presence of
CpG island, (3) H. pylori infection in non-cancerous gastric mucosa and (4) LOH
status in cancer. These findings are quite interesting and important, although the
first and second points are already described in their previous reports. However,
there are several concerns as listed below, which requires revision of this
manuscript before acceptance.
Major Compulsory Revisions
1. Does methylation in the transitional CpG sites correlate with gene expression
in the specimens used in this study? Only the SAGE tag results in normal
stomach is shown, and this point is not mentioned.
2. Is there any correlation between the transitional CpG sites methylation and
neighboring CpG island methylation? It is of interest to see whether CpG islands
are methylated or not, when the neighboring transitional CpG sites are
methylated by H. pylori infection.
3. Page 18: Are there any functional evidence for the statement "In cancer tissue
that undergoes the LOH event that reduces a gene dose, the remaining gene
copies have the increased possibility of using the nuclear proteins and this would
lead to the demethylation of transitional-CpG segments"? If so, please include a
citation for this statement. If not, please show functional evidence that
hypomethylation is a consequence of LOH in cancer.
4. Page 21: "This study suggests that the concurrent methylation of multiple
CpGisland genes initiates and sustains the adaptive differentiation of newly fixed
stem cells in the gastric mucosa infected with H. pylori, and that the LOH-induced
DNA demethylation and discordant methylation of stomach-specific genes may
facilitate gastric carcinogenesis by reactivating a stem-cell intrinsic program."
This study does not provide enough functional evidences to draw this conclusion.
Minor Essential Revisions
5. "Overmethylation" and "Undermethylation" are not commonly used terms to
describe DNA methylation, and the authors have used "hypermethylation" and
"hypomethylation" in their previous manuscript (Kim YH et al. BMC Cancer,
2006). Is there any specific reason to use these uncommon terms in this
manuscript?
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests.
assistant