Reviewer's report
Title:Telomere shortening correlates to dysplasia but not to DNA aneuploidy in
longstanding ulcerative colitis
Version: 4Date:10 October 2013
Reviewer: Junko Aida
Reviewer's report:
Major Compulsory Revisions
In order to examine telomere biology in preneoplastic lesions from patients with
long-standing ulcerative colitis (UC), the authors analyzed multiple biopsy
specimens from colectomy materials harboring dysplasia and DNA aneuploidy.
They assessed the amount of ultra-short telomeres using the Universal STELA
method, and the mean telomere length using q-PCR, and were able to
demonstrate associations between ultra-short telomeres and neoplastic
development in UC. However, the approach employed by the authors has four
inherent problems related to examination of telomere length in the context of
human disease.
(1) There is no way of specifying the type of cell used for telomere measurement,
because the authors used specimens of the entire colonic mucosa, which is
constituted by many cell types. Thus, the mean telomere length would depend on
the relative ratios of the various types of cells present. Therefore I wonder
whether it is meaningful to make comparisons between the cases that have
different cell constitution ratios.
(2) Did the authors evaluate the degree of inflammation in UC cases? Infiltration
of many inflammatory cells effects on mean telomere length of the tissue.
(3) Telomeres shorten with aging. Therefore there is a need to consider age of
the patients from whom the tissue samples were taken.
(4) The telomere lengths of tissue or cells, or chromosomes, vary and show a
non-normal distribution. From a statistical standpoint, it can be considered that
the median or modal value would be more suitable than the mean value for
estimation of telomere length. Did the authors consider using the median or
modal value?
Minor Essential Revisions
(i) p.4, l.1: ‘ROS’ is the abbreviation for ‘reactive oxygen species’, and not
‘oxidative stress’; ‘ROS’ is used only twice in the manuscript. So I think that there
is no need to use the abbreviation ‘ROS’ in the manuscript.
(ii) p.8, l.23: What does the abbreviation ‘T/S ratio’ stand for?
(iii) Is ‘scg’ on p.9, l.3 and l.7 the same as ‘SCG’ on p.17, l.23? This abbreviation
is not defined at first mention in the text.
(iv) p.18, l.23: There is no need to use the abbreviation ‘BFB’ for
breakage-fusion-bridge.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:Telomere shortening correlates to dysplasia but not to DNA aneuploidy in
longstanding ulcerative colitis
Version: 4Date:10 October 2013
Reviewer: Junko Aida
Reviewer's report:
Major Compulsory Revisions
In order to examine telomere biology in preneoplastic lesions from patients with
long-standing ulcerative colitis (UC), the authors analyzed multiple biopsy
specimens from colectomy materials harboring dysplasia and DNA aneuploidy.
They assessed the amount of ultra-short telomeres using the Universal STELA
method, and the mean telomere length using q-PCR, and were able to
demonstrate associations between ultra-short telomeres and neoplastic
development in UC. However, the approach employed by the authors has four
inherent problems related to examination of telomere length in the context of
human disease.
(1) There is no way of specifying the type of cell used for telomere measurement,
because the authors used specimens of the entire colonic mucosa, which is
constituted by many cell types. Thus, the mean telomere length would depend on
the relative ratios of the various types of cells present. Therefore I wonder
whether it is meaningful to make comparisons between the cases that have
different cell constitution ratios.
(2) Did the authors evaluate the degree of inflammation in UC cases? Infiltration
of many inflammatory cells effects on mean telomere length of the tissue.
(3) Telomeres shorten with aging. Therefore there is a need to consider age of
the patients from whom the tissue samples were taken.
(4) The telomere lengths of tissue or cells, or chromosomes, vary and show a
non-normal distribution. From a statistical standpoint, it can be considered that
the median or modal value would be more suitable than the mean value for
estimation of telomere length. Did the authors consider using the median or
modal value?
Minor Essential Revisions
(i) p.4, l.1: ‘ROS’ is the abbreviation for ‘reactive oxygen species’, and not
‘oxidative stress’; ‘ROS’ is used only twice in the manuscript. So I think that there
is no need to use the abbreviation ‘ROS’ in the manuscript.
(ii) p.8, l.23: What does the abbreviation ‘T/S ratio’ stand for?
(iii) Is ‘scg’ on p.9, l.3 and l.7 the same as ‘SCG’ on p.17, l.23? This abbreviation
is not defined at first mention in the text.
(iv) p.18, l.23: There is no need to use the abbreviation ‘BFB’ for
breakage-fusion-bridge.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Telomere shortening correlates to dysplasia but not to DNA aneuploidy in
longstanding ulcerative colitis
Version: 4Date:10 October 2013
Reviewer: Junko Aida
Reviewer's report:
Major Compulsory Revisions
In order to examine telomere biology in preneoplastic lesions from patients with
long-standing ulcerative colitis (UC), the authors analyzed multiple biopsy
specimens from colectomy materials harboring dysplasia and DNA aneuploidy.
They assessed the amount of ultra-short telomeres using the Universal STELA
method, and the mean telomere length using q-PCR, and were able to
demonstrate associations between ultra-short telomeres and neoplastic
development in UC. However, the approach employed by the authors has four
inherent problems related to examination of telomere length in the context of
human disease.
(1) There is no way of specifying the type of cell used for telomere measurement,
because the authors used specimens of the entire colonic mucosa, which is
constituted by many cell types. Thus, the mean telomere length would depend on
the relative ratios of the various types of cells present. Therefore I wonder
whether it is meaningful to make comparisons between the cases that have
different cell constitution ratios.
(2) Did the authors evaluate the degree of inflammation in UC cases? Infiltration
of many inflammatory cells effects on mean telomere length of the tissue.
(3) Telomeres shorten with aging. Therefore there is a need to consider age of
the patients from whom the tissue samples were taken.
(4) The telomere lengths of tissue or cells, or chromosomes, vary and show a
non-normal distribution. From a statistical standpoint, it can be considered that
the median or modal value would be more suitable than the mean value for
estimation of telomere length. Did the authors consider using the median or
modal value?
Minor Essential Revisions
(i) p.4, l.1: ‘ROS’ is the abbreviation for ‘reactive oxygen species’, and not
‘oxidative stress’; ‘ROS’ is used only twice in the manuscript. So I think that there
is no need to use the abbreviation ‘ROS’ in the manuscript.
(ii) p.8, l.23: What does the abbreviation ‘T/S ratio’ stand for?
(iii) Is ‘scg’ on p.9, l.3 and l.7 the same as ‘SCG’ on p.17, l.23? This abbreviation
is not defined at first mention in the text.
(iv) p.18, l.23: There is no need to use the abbreviation ‘BFB’ for
breakage-fusion-bridge.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
assistant