Disequilibrium between BRCA1 and BRCA2 Circular and Messenger RNAs Plays a Role in Breast Cancer
, Marick Laé 2,3, Philippe Ruminy 2 and Claude Houdayer 5,*Round 1
Reviewer 1 Report
In the manuscript entitled "Disequilibrium between BRCA1 and BRCA2 circular and messenger RNAs plays a role in breast cancer" described by the authors an innovative, simple and high throughput method for simultaneous detection of splicing and backsplicing, validated and applied in a series of FFPE samples, which can be easily translated in diagnostics. Secondly, they demonstrated for BRCA1 and BRCA2 a disequilibrium in the circRNA/mRNA ratio between tumour and normal breast tissues. The authors also suggested that a disequilibrium between BRCA1/2 circular and messenger RNAs in favour of mRNA could reflect a tentative adaptation to tumorigenesis. The method described by the authors seems to have several strengths: the test requires 2 days for the entire procedure, no specific materials or platforms are required, the cost per sample is not high, low quality and quantity of input RNA is required.
The elaborate is well structured and full of references, giving the work a good quality in the presentation. The images are schematically well done and their legends are clear, even the tables and supplementary files are complete.
The manuscript is considered eligible for publication in CANCERS
Author Response
We warmly thank the reviewer for the rapid response and the positives comments on the study.
C Houdayer and C Levacher, on behalf of the team
Reviewer 2 Report
In this manuscript, the authors investigated how balanced disruption between circRNAs and mRNAs could promote breast cancer. The author has developed an innovative assay for the simultaneous study of circRNAs and mRNAs, called Splice and Expression Analyses by exon Ligation and High Throughput Sequencing (SEALigTHS). The author has investigated an independent research set of 95 pairs of tumors and adjacent 30 normal breast tissues and found ratios of BRCA1 and BRCA2 circRNAs/mRNAs were significantly lower in tumor breast tissue compared to normal tissues. The further author has demonstrated for the first time that a disequilibrium between BRCA1 and BRCA2 circRNAs and mRNAs plays a role in breast cancer. SEALigTHS technique looks very innovative and robust to simultaneous study backsplicing and linear splicing. The manuscript is well-written, useful for readers in the field, and can be accepted for publication.
Author Response
We warmly thank the reviewer for the rapid response and the positives comments on the study.
C Houdayer and C Levacher, on behalf of the team
