Reviewer's report 
 Alterations of tumor suppressor gene p16INK4A in pancreatic ductal carcinoma Title: 
 1  21 February 2005 Version: Date: 
 aldo scarpa Reviewer: 
Reviewer's report: 
General 
The manuscript by Sharma et al describes the analysis of p16 in a series of primary pancreatic 
ductal cancers. In particular, the authors evaluated the mutational and methylation status as well as the presence of homozygous deletions and immunohistochemical status. The authors found a proportion of mutated cases and cases with homozygous deletions in proportions similar to 
previously published series, although the frequency of methylation was significantly higher than 
previous reports. The paper is acceptably written. 
The report addresses the paucity of data about p16 status in primary pancreatic adenocarcinoma, 
especially in an Asian population. 
------------------------------------------------------------------------------- Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
1. With regards to the assay for homozygous deletion, this reviewer is somewhat perplexed by the 
author’s statement that the primary cancers used for analysis of homozygous deletion contained more than 90% tumors cells, which would seem rather unusual considering that these were primary pancreatic ductal cancers. In fact, cancer cellularity in this type of cancer is notably very low in the 
vast majority of cases. Perhaps the authors could comment on this. 
------------------------------------------------------------------------------ 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
The authors also might wish to make some commentary on the differences in methylation frequency 
observed, especially in the light of a previous report suggesting that geographic variations in the 
methylation status of various CpG islands indicate that environmental factors may be responsible for 
these differences (J Natl Cancer Inst. 2002 May 15;94(10):755). ------------------------------------------------------------------------------- Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Reviewer's report 
 Alterations of tumor suppressor gene p16INK4A in pancreatic ductal carcinoma Title: 
 1  21 February 2005 Version: Date: 
 aldo scarpa Reviewer: 
Reviewer's report: 
General 
The manuscript by Sharma et al describes the analysis of p16 in a series of primary pancreatic 
ductal cancers. In particular, the authors evaluated the mutational and methylation status as well as the presence of homozygous deletions and immunohistochemical status. The authors found a proportion of mutated cases and cases with homozygous deletions in proportions similar to 
previously published series, although the frequency of methylation was significantly higher than 
previous reports. The paper is acceptably written. 
The report addresses the paucity of data about p16 status in primary pancreatic adenocarcinoma, 
especially in an Asian population. 
------------------------------------------------------------------------------- Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
1. With regards to the assay for homozygous deletion, this reviewer is somewhat perplexed by the 
author’s statement that the primary cancers used for analysis of homozygous deletion contained more than 90% tumors cells, which would seem rather unusual considering that these were primary pancreatic ductal cancers. In fact, cancer cellularity in this type of cancer is notably very low in the 
vast majority of cases. Perhaps the authors could comment on this. 
------------------------------------------------------------------------------ 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
The authors also might wish to make some commentary on the differences in methylation frequency 
observed, especially in the light of a previous report suggesting that geographic variations in the 
methylation status of various CpG islands indicate that environmental factors may be responsible for 
these differences (J Natl Cancer Inst. 2002 May 15;94(10):755). ------------------------------------------------------------------------------- Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
Please review this paper.
user
Reviewer's report 
 Alterations of tumor suppressor gene p16INK4A in pancreatic ductal carcinoma Title: 
 1  21 February 2005 Version: Date: 
 aldo scarpa Reviewer: 
Reviewer's report: 
General 
The manuscript by Sharma et al describes the analysis of p16 in a series of primary pancreatic 
ductal cancers. In particular, the authors evaluated the mutational and methylation status as well as the presence of homozygous deletions and immunohistochemical status. The authors found a proportion of mutated cases and cases with homozygous deletions in proportions similar to 
previously published series, although the frequency of methylation was significantly higher than 
previous reports. The paper is acceptably written. 
The report addresses the paucity of data about p16 status in primary pancreatic adenocarcinoma, 
especially in an Asian population. 
------------------------------------------------------------------------------- Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
1. With regards to the assay for homozygous deletion, this reviewer is somewhat perplexed by the 
author’s statement that the primary cancers used for analysis of homozygous deletion contained more than 90% tumors cells, which would seem rather unusual considering that these were primary pancreatic ductal cancers. In fact, cancer cellularity in this type of cancer is notably very low in the 
vast majority of cases. Perhaps the authors could comment on this. 
------------------------------------------------------------------------------ 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the 
author can be trusted to correct) 
The authors also might wish to make some commentary on the differences in methylation frequency 
observed, especially in the light of a previous report suggesting that geographic variations in the 
methylation status of various CpG islands indicate that environmental factors may be responsible for 
these differences (J Natl Cancer Inst. 2002 May 15;94(10):755). ------------------------------------------------------------------------------- Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article whose findings are important to those with closely related research Level of interest: 
interests 
 Acceptable Quality of written English: 
 No Statistical review: 
assistant