Reviewer's report
Title:Telomere shortening correlates to dysplasia but not to DNA aneuploidy in
longstanding ulcerative colitis
Version:5Date:6 December 2013
Reviewer: Rosana Risques
Reviewer's report:
The authors have successfully addressed most of the comments. Only a few
minor revisions remain.
Minor Essential Revisions
1. The fact that all aneuploid samples except two included only 5-10% aneuploid
cells is crucial and should be specifically mentioned in the Discussion. Currently
it just talks about admixture of diploid cells, but this admixture is actually 90 or
95% diploid cells!
2. The authors might want to review this suggestion in discussion: “ultra-short
telomeres might develop independently from the shortening mean telomere
length”. Most likely oxidative damage shortens telomeres, which leads to
ultra-short telomeres as well as to a decrease of the mean telomere length.
However, because the mean is a composite measure of all the telomeres, it does
not capture that well the presence of one or a few critically short telomeres. The
STELA technique does and, thus, it is a more accurate estimator of the
progression towards dysplasia and cancer, which appears to occur when
critically short telomeres fail to cap the end of the chromosomes, leading to
cycles of bridge-breakage-fusion and chromosomal instability.
Discretionary revisions
1. In Discussion, an alternative explanation for the ‘rather surprising finding of no
significant difference in mean telomere length between progressors and non
progressors’ might be the small number of patients coupled with a rather high
coefficient of variation for mean telomere length measurement with either of the
single control genes (10.5% and 11.3%). Typical CV for Q-PCR telomere length
is between 6-7% (see for instance PMID: 21824912). A potential reason for high
CV in this study is the use of a 7900HT Fast Real-Time PCR System, which
appears to have a plate position effect that might increase variability, especially
in samples run in the edges of the plates.
2. The results and parts of the discussion are still somehow difficult to follow due
to so many comparisons. Additional figures or tables summarizing the results
would be helpful, but not essential.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Reviewer's report
Title:Telomere shortening correlates to dysplasia but not to DNA aneuploidy in
longstanding ulcerative colitis
Version:5Date:6 December 2013
Reviewer: Rosana Risques
Reviewer's report:
The authors have successfully addressed most of the comments. Only a few
minor revisions remain.
Minor Essential Revisions
1. The fact that all aneuploid samples except two included only 5-10% aneuploid
cells is crucial and should be specifically mentioned in the Discussion. Currently
it just talks about admixture of diploid cells, but this admixture is actually 90 or
95% diploid cells!
2. The authors might want to review this suggestion in discussion: “ultra-short
telomeres might develop independently from the shortening mean telomere
length”. Most likely oxidative damage shortens telomeres, which leads to
ultra-short telomeres as well as to a decrease of the mean telomere length.
However, because the mean is a composite measure of all the telomeres, it does
not capture that well the presence of one or a few critically short telomeres. The
STELA technique does and, thus, it is a more accurate estimator of the
progression towards dysplasia and cancer, which appears to occur when
critically short telomeres fail to cap the end of the chromosomes, leading to
cycles of bridge-breakage-fusion and chromosomal instability.
Discretionary revisions
1. In Discussion, an alternative explanation for the ‘rather surprising finding of no
significant difference in mean telomere length between progressors and non
progressors’ might be the small number of patients coupled with a rather high
coefficient of variation for mean telomere length measurement with either of the
single control genes (10.5% and 11.3%). Typical CV for Q-PCR telomere length
is between 6-7% (see for instance PMID: 21824912). A potential reason for high
CV in this study is the use of a 7900HT Fast Real-Time PCR System, which
appears to have a plate position effect that might increase variability, especially
in samples run in the edges of the plates.
2. The results and parts of the discussion are still somehow difficult to follow due
to so many comparisons. Additional figures or tables summarizing the results
would be helpful, but not essential.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Please review this paper.
user
Reviewer's report
Title:Telomere shortening correlates to dysplasia but not to DNA aneuploidy in
longstanding ulcerative colitis
Version:5Date:6 December 2013
Reviewer: Rosana Risques
Reviewer's report:
The authors have successfully addressed most of the comments. Only a few
minor revisions remain.
Minor Essential Revisions
1. The fact that all aneuploid samples except two included only 5-10% aneuploid
cells is crucial and should be specifically mentioned in the Discussion. Currently
it just talks about admixture of diploid cells, but this admixture is actually 90 or
95% diploid cells!
2. The authors might want to review this suggestion in discussion: “ultra-short
telomeres might develop independently from the shortening mean telomere
length”. Most likely oxidative damage shortens telomeres, which leads to
ultra-short telomeres as well as to a decrease of the mean telomere length.
However, because the mean is a composite measure of all the telomeres, it does
not capture that well the presence of one or a few critically short telomeres. The
STELA technique does and, thus, it is a more accurate estimator of the
progression towards dysplasia and cancer, which appears to occur when
critically short telomeres fail to cap the end of the chromosomes, leading to
cycles of bridge-breakage-fusion and chromosomal instability.
Discretionary revisions
1. In Discussion, an alternative explanation for the ‘rather surprising finding of no
significant difference in mean telomere length between progressors and non
progressors’ might be the small number of patients coupled with a rather high
coefficient of variation for mean telomere length measurement with either of the
single control genes (10.5% and 11.3%). Typical CV for Q-PCR telomere length
is between 6-7% (see for instance PMID: 21824912). A potential reason for high
CV in this study is the use of a 7900HT Fast Real-Time PCR System, which
appears to have a plate position effect that might increase variability, especially
in samples run in the edges of the plates.
2. The results and parts of the discussion are still somehow difficult to follow due
to so many comparisons. Additional figures or tables summarizing the results
would be helpful, but not essential.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
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