Genetic Characterization in High-Risk Individuals from a Low-Resource City of Peru
, Nelly Solis 1, Maria Isabel Palacios 2, Liz Elva Zevallos-Escobar 2, Edison Vasquez Corales 2, Juan Carlos Bazo-Alvarez 3,4, Constantino Dominguez-Barrera 5, Anthony Campos 5, Patrik Wernhoff 6, Per Olaf Ekstrøm 7, Pål Møller 7, Tina Visnovska 8, Eivind Hovig 7,9, Janina Balazar-Palacios 10, Karin Alvarez-Valenzuela 11, Sigve Nakken 7,9,12 and Mev Dominguez-Valentin 7,*Round 1
Reviewer 1 Report (Previous Reviewer 3)
The essence of the suggestions were not satisfied. The MS should express the emphasis to be suggested, based the genetic findings described, for the improvement in the attention to the population of Chimbote, as a conclusion from the diagnosis in, the even few cases, with very actionable genes.
Reviewer 2 Report (Previous Reviewer 1)
Dear Authors,
I am convinced that all points of the reviewers are properly addressed.
Thank you for excellent revision
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
Dear Authors,
I have read the paper with great interest. The study is well designed and the topic is of high scientific value and considerable clinical relevance to health policy for a country in Latin America. Therefore, I endorse the publication, even if it is of secondary importance at the international level.
The main question addressed to the research project is which cancer-predisposing germline variants and variants of unclear significance occur with what prevalence in high-risk patients of a low-resource Peruvian city.
The topic is indeed original and also relevant. The rationale is that, apparently for the first time in a Latin American setting with few resources, costly studies are being conducted that are more common in regions of the world with more developed health care systems.
The work is a supplement to other published material.
The methodology is appropriately chosen. In my opinion, no further methodological improvements are required.
The tables are clear and detailed. The illustrations are understandable and informative.
Reviewer 2 Report
The authors perform a panel of 94 genes in 84 Peruvian individuals. They identified a total of 23% of individuals with germline pathogenic variants in predisposing genes probably having an impact in their genetic conselling and clinical management.
The manuscript is well-structured and easy to read. I have no major concerns about the contents of the manuscript. Below are reported comments that will improve the contents of the manuscript:
Abstract (line 39): Change the gene name SDBS to SBDS.
Table 2: Title is missing.
Results and Table 2: Add final ACMG classification (P/LP/VUS/LB/B) and evidences (codes applied following ACMG guidelines).
Figure 3 (title): Indicate the meaning of "+".
Figure 3 (a): Names are not readables, change their orientation or the letters size.
Figure 3 (b): Add "+" to the pedigree.
Reviewer 3 Report
1) The MS “Comprehensive characterization of hereditary cancer cases from Peru: Bringing precision medicine to a low-resource setting city” has the intention of describing “genetic testing for hereditary cancers is inconsistently applied within the healthcare systems in Latin America. The prevalence and spectrum of cancer-predisposing germline variants is thus poorly characterized in these populations”, to be remarked is that the qualification of what is known about hereditary cancers should be restricted to the country or area in which the work is developed and/or the data is collected; the generalization extension to other areas/countries/continent it is risky and also may not reflect the real panorama.
2) The “comprehensive” and the “precision medicine” concepts as in the title, are is not reflected in the content along the procedures described with the patients. The genetic findings well sustain the application of precision medicine measures, although the 84 individuals are a rather few studies.
3) The methods need to be expanded in specifying with quality values to assure the best analysis of the samples.
4) The total number of the population of the area/s is necessary to bring the % of individuals reached in this study (Northern Peru, Chimbote?). Mostly, since nowadays it is a low amount the 84 individuals analyzed.
5) The TP53 variant is silent and pathogenic because of the spliceogenic position, a data that should be stated as reflected in the title of the 1998 reference.
6) The variant in the protooncogene RET is associated with medullary thyroid carcinoma, an infrequent thyroid cancer, it is important to be clarified in the text.
7) A table with the subjects analyzed and the data described in table 1 is very depicting of the population analyzed, with the addition of a column with the % of individuals with a pathogenic variant detected, while the last two columns are irrelevant. Table 1 may be improved with a less redundant title.
