Reviewer's report 
 Stability of Age-related Colon Stem Cell Methylation After Neo-adjuvant Therapy in a Patient Title: 
with Attenuated Familial Adenomatous Polyposis 
 1  3 April 2005 Version: Date: 
 Minoru Toyota Reviewer: 
Reviewer's report: 
General 
In this manuscript, Kim et al examined methylation status of two CpG rich regions in colorectal crypts 
from the patient with attenuated familial adenomatous polyposis. Using the DNA obtained before 
and after chemotherapy, they found that environmental changes did not significantly affect crypt 
methylation pattern. They concluded that age-related methylation reflects epigenetic errors in stem 
cells that slowly accumulate in a clock-like manner. Overall, experiments were well done, and the interpretations and conclusions are clearly presented. The information shown in this manuscript may 
be useful for the readers of BMC Gastroenterology. In suitability of publication, several important 
issues as below to be solved. 
Specific points. 
1. The authors examined two CpG rich regions they term CSX and BGN. The authors should 
describe these two regions in more detail. 
2. The authors concluded that age-related methylation in stem cell is not affected by environmental 
changes. However, there is no description about age-related methylation of CSX and BGN in this 
manuscript. Because the patients they examined is 22 years old, the methylation may they examined 
may not be associated with aging. One plausible way is to change the title to “Stability of colon stem 
cell methylation after neo-adjuvant therapy in …..”. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
Reviewer's report 
 Stability of Age-related Colon Stem Cell Methylation After Neo-adjuvant Therapy in a Patient Title: 
with Attenuated Familial Adenomatous Polyposis 
 1  3 April 2005 Version: Date: 
 Minoru Toyota Reviewer: 
Reviewer's report: 
General 
In this manuscript, Kim et al examined methylation status of two CpG rich regions in colorectal crypts 
from the patient with attenuated familial adenomatous polyposis. Using the DNA obtained before 
and after chemotherapy, they found that environmental changes did not significantly affect crypt 
methylation pattern. They concluded that age-related methylation reflects epigenetic errors in stem 
cells that slowly accumulate in a clock-like manner. Overall, experiments were well done, and the interpretations and conclusions are clearly presented. The information shown in this manuscript may 
be useful for the readers of BMC Gastroenterology. In suitability of publication, several important 
issues as below to be solved. 
Specific points. 
1. The authors examined two CpG rich regions they term CSX and BGN. The authors should 
describe these two regions in more detail. 
2. The authors concluded that age-related methylation in stem cell is not affected by environmental 
changes. However, there is no description about age-related methylation of CSX and BGN in this 
manuscript. Because the patients they examined is 22 years old, the methylation may they examined 
may not be associated with aging. One plausible way is to change the title to “Stability of colon stem 
cell methylation after neo-adjuvant therapy in …..”. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
Please review this paper.
user
Reviewer's report 
 Stability of Age-related Colon Stem Cell Methylation After Neo-adjuvant Therapy in a Patient Title: 
with Attenuated Familial Adenomatous Polyposis 
 1  3 April 2005 Version: Date: 
 Minoru Toyota Reviewer: 
Reviewer's report: 
General 
In this manuscript, Kim et al examined methylation status of two CpG rich regions in colorectal crypts 
from the patient with attenuated familial adenomatous polyposis. Using the DNA obtained before 
and after chemotherapy, they found that environmental changes did not significantly affect crypt 
methylation pattern. They concluded that age-related methylation reflects epigenetic errors in stem 
cells that slowly accumulate in a clock-like manner. Overall, experiments were well done, and the interpretations and conclusions are clearly presented. The information shown in this manuscript may 
be useful for the readers of BMC Gastroenterology. In suitability of publication, several important 
issues as below to be solved. 
Specific points. 
1. The authors examined two CpG rich regions they term CSX and BGN. The authors should 
describe these two regions in more detail. 
2. The authors concluded that age-related methylation in stem cell is not affected by environmental 
changes. However, there is no description about age-related methylation of CSX and BGN in this 
manuscript. Because the patients they examined is 22 years old, the methylation may they examined 
may not be associated with aging. One plausible way is to change the title to “Stability of colon stem 
cell methylation after neo-adjuvant therapy in …..”. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
 Accept after minor essential revisions What next?: 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests. 
assistant