Reviewer ’s report  
 
Title:  Therapy susceptible germline -related BRCA 1 -mutation in a case  of metastasized mixed 
adeno -neuroendocrine carcinoma (MANEC) of the small bowel  
 
Version: 0 Date: 30 Jan 2018 
 
Reviewer:  Huang  WY 
 
Reviewer’s report:  
 
This manuscript describes details about the identification of BRAC1/2 mutation in small 
intestinal MANEC. The results of NGS sequencing and clinical responses to treatment are 
convincing.  
 
The major issue is pathological diagnosis of MANEC. From the submitted fissure 1, I can not 
appreciate it i s a MANEC. A paragraph describing the histopathology of tumor is required. The 
authors need to include better figures of MANEC for future submission.  
 
 
Minor:  
 
(1) The method on NGS can be shortened.  
 
(2) What are the other 12 genes tested? Please list other mutations identified.  
 
(3) Please list the full name of PARP  
 
(4) Author CH's contribution includes statistical analysis. Where is statistical analysis in this 
manuscript?  
 
Are the methods appropria te and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusion s drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose finan cially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hol d or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the  above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declar e that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name wi ll be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available un der an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title:  Therapy susceptible germline -related BRCA 1 -mutation in a case  of metastasized mixed 
adeno -neuroendocrine carcinoma (MANEC) of the small bowel  
 
Version: 0 Date: 30 Jan 2018 
 
Reviewer:  Huang  WY 
 
Reviewer’s report:  
 
This manuscript describes details about the identification of BRAC1/2 mutation in small 
intestinal MANEC. The results of NGS sequencing and clinical responses to treatment are 
convincing.  
 
The major issue is pathological diagnosis of MANEC. From the submitted fissure 1, I can not 
appreciate it i s a MANEC. A paragraph describing the histopathology of tumor is required. The 
authors need to include better figures of MANEC for future submission.  
 
 
Minor:  
 
(1) The method on NGS can be shortened.  
 
(2) What are the other 12 genes tested? Please list other mutations identified.  
 
(3) Please list the full name of PARP  
 
(4) Author CH's contribution includes statistical analysis. Where is statistical analysis in this 
manuscript?  
 
Are the methods appropria te and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusion s drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose finan cially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hol d or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the  above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declar e that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name wi ll be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available un der an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title:  Therapy susceptible germline -related BRCA 1 -mutation in a case  of metastasized mixed 
adeno -neuroendocrine carcinoma (MANEC) of the small bowel  
 
Version: 0 Date: 30 Jan 2018 
 
Reviewer:  Huang  WY 
 
Reviewer’s report:  
 
This manuscript describes details about the identification of BRAC1/2 mutation in small 
intestinal MANEC. The results of NGS sequencing and clinical responses to treatment are 
convincing.  
 
The major issue is pathological diagnosis of MANEC. From the submitted fissure 1, I can not 
appreciate it i s a MANEC. A paragraph describing the histopathology of tumor is required. The 
authors need to include better figures of MANEC for future submission.  
 
 
Minor:  
 
(1) The method on NGS can be shortened.  
 
(2) What are the other 12 genes tested? Please list other mutations identified.  
 
(3) Please list the full name of PARP  
 
(4) Author CH's contribution includes statistical analysis. Where is statistical analysis in this 
manuscript?  
 
Are the methods appropria te and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusion s drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose finan cially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hol d or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the  above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declar e that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name wi ll be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available un der an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant