Review for 10.1186/s12876-020-01403-y (2020)

Reviewer’ s report
Title: Germline RAD54L with Somatic POLE Defect Implicated in Hypermutation Phenotype:
Case presentation
Version: 0Date: 27 May 2020
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
RELEV ANCE - Does this case report make a contribution to medical knowledge, have
educational value, or highlight the need for a change in clinical practice or diagnostic/prognosticapproaches?Yes, this report contributes to medical knowledge
CASE DESCRIPTION - Are the details of the case sufficiently well described to understand the
patient's symptoms and course of treatment?No - there are minor issues
DIAGNOSIS/INTERPRETATION - Based on the facts presented, are the diagnosis, interpretation,
and course of treatment medically sound?No, based on information contained in the report, the authors' interpretation of this case is unsound
DISCUSSION OF THE CASE - Does the discussion appropriately analyse the importance of the
findings and their relevance to future understanding of disease processes, diagnosis or treatment?Has an adequate literature review pertinent to the case been included?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Could an appropriately REVISED version of this
work represent a technically sound contribution?Probably - with minor revisions
PEER REVIEWER COMMENTS:GENERAL COMMENTS: The authors present a case report about one patient with colon cancer
with a heterozygous frameshift mutation in RAD54L gene. The authors claim it is a germlinemutation, whereas they found during the analysis of tumor material. They should make it clear thatthey verified in the constitutional cells of the patient and should also report the genomiccoordinates of the mutation. Moreoer, they report in the title that the constitutional mutation isinherited, but they never mention if any of the two parents was tested. Was the carrier thenscreened for colon cancer?In addition, they found a POLE somatic mutation P286R in the exonuclease domain of the geneand by combining the two results (constitutional and somatic) they present a novel mechanism ofcolon carcinogenesis.
The hypothesis is very interesting and well described, but the report, based on a single case, needs
a more cautious approach.The variant the authors find is not known in a gene which is substantially not known. The authorsbring some arguments in support of the pathogenicity of the RAD54L variant, but the causalitylink to the tumor phenotype is missing. The authors should consider to smooth their message. Tofind more elements in favor of the new gene, the authors could mention also if the tumor, whichwas MSS but with a high rate of mutations, showed elevated microsatellite alterations at selectedtetranucleotide repeats (EMAST), which could direct to a constitutional repair defectThe english language is simple but correct
REQUESTED REVISIONS:
Clarify if the variant is really inherited or not; specify the genomic coordinates of the variant;report if the tumor showed elevated microsatellite alterations at selected tetranucleotide repeats(EMAST); judge more cautiously the RAD54L and POLE association
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
NoDoes the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
YesAre the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
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 furtherassessment in your comments to the editors.
Not relevant to this manuscriptQuality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being publishedDeclaration of competing interests
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