CDKN2A/B Homozygous Deletions in Astrocytomas: A Literature Review

Round 1

Reviewer 1 Report

The review titled: “CDKN2A/B homozygous deletions in astrocytomas: A literature review” is an interesting manuscript because genomic alterations of CDKN2A/B, in astrocytomas is an important research focus.

The authors report a detailed literature, analysing important points of scientific research in the field.

The manuscript is well structured and the data are well illustrated and deserves to be published on Current issues in molecular biology.

Author Response

Comment

The review titled: “CDKN2A/B homozygous deletions in astrocytomas: A literature review” is an interesting manuscript because genomic alterations of CDKN2A/B, in astrocytomas is an important research focus.

The authors report a detailed literature, analysing important points of scientific research in the field.

The manuscript is well structured and the data are well illustrated and deserves to be published on Current issues in molecular biology.

 

Response

Thank you for reviewing our article. We are pleased that you agree with the pertinence of this review.

Reviewer 2 Report

The manuscript focuses on systemic revision of literature data about the role ofCDKN2A/B homozygous deletions in astrocytomas patients. Particularly, the manuscript is based on the analysis of clinical role of this biomarker in a specific tumro setting. Accordingly, the manuscript is timely relevant and technically correct. I would suggest some minor modifications to improve the readibility of the manuscript

 

- In the text, please, could the authors also show if other type of CDKN2A/B related alterations may be also usefull to startify CNS patients? Could the authors also verify if this biomarker may be alterated in other tumor setting?

 

- Please, could the authors implement table 1 with technical parameters as sensitivity and specificity in order to improve the readibility of the table?

 

- Please, could the authors describe in a dedicated section technical parameters that could be available for this molecular testing?

The manuscript focuses on systemic revision of literature data about the role ofCDKN2A/B homozygous deletions in astrocytomas patients. Particularly, the manuscript is based on the analysis of clinical role of this biomarker in a specific tumro setting. Accordingly, the manuscript is timely relevant and technically correct. I would suggest some minor modifications to improve the readibility of the manuscript

Author Response

Thank you for the excellent suggestions regarding our review, which has prompted us to make the below changes.

 

Comment 1

In the text, please, could the authors also show if other type of CDKN2A/B related alterations may be also useful to stratify CNS patients? Could the authors also verify if this biomarker may be alterated in other tumor setting?

Response 1

We agree that the review does not fully address all CDKN2A/B  alterations and this could be improved upon. We have therefore highlighted other alterations mentioned in the review in section 6 entitled :Putting CDKN2A/B Deletions into Perspective”, lines 459-464:

“It should be noted that point mutations were also highlighted by some of the presented research. However the evidence for this particular alteration is very limited and does not show an impact on survival. Again as these alterations do not result in the loss of genes neighbouring CDKN2A/B, this may also indicate an importance of these bystander genes in outcomes for astrocytomas with CDKN2A/B deletions.”

The loss of CKDN2A has been identified in other malignancies and we have attempted to acknowledge this in section 2 entitled “Normal role of CDKN2A/B and effect of their deletion”, lines 126-129:

“Reflecting this, inactivation of CDKN2A function has been reported in a variety of other malignancies including breast cancer, lung cancer, head and neck cancer, melanoma and bladder cancer (9).”

 

Comment 2

Please, could the authors implement table 1 with technical parameters as sensitivity and specificity in order to improve the readability of the table?

Response 2

We agree that the technical parameters in table 1 would improve its presentation. Unfortunately, we have previously attempted this and due to major heterogeneity in methods used and in reported results it was not possible and added further confusion.

 

Comment 3

Please, could the authors describe in a dedicated section technical parameters that could be available for this molecular testing?

Response 3

Due to the issues with heterogeneity discussed in response 2, we are unable to have a dedicated section for technical parameters. However, we agree this is important and have acknowledged these limitations in section 3 entitled "Identification of CDKN2A/B Deletions" where we have discussed technical parameters as best we can within these limitations. The changes are as follows, lines 178-182:

“It should be noted that the accuracy of these variety of methods depend on the specific as-say types used, as the genomic / cytogenetic resolution of each method differs. We are therefore unable to uniformly describe technical parameters of each method, but have at-tempted to give an overview where possible.”

Round 2

Reviewer 2 Report

The manuscript may be accepted in the present form