In this report we described the case of a BRCA1/2 (BRCA) molecular testing performed on tumor sample in a High Grade Serous Ovarian Cancer (HGSOC) patient with two different Next Generation Tumor Sequencing (NGTS) pipelines. The two clinical reports leaded to apparently different BRCA status, providing important foods for thought. After NGTS, the gene sequencing information (i.e., reads) are aligned to the reference gene sequences obtained from public databases, in order to provide an uniform nomenclature for unambiguous variant designation. However, the criteria adopted for variant reporting in tissue test are not always univocal. Particularly, this is the case of rare and unclassified BRCA variants for which the molecular evaluation may be a relevant challenge. Here we described a BRCA1 unclassified variant that may be re-evaluated in the context of alternative BRCA1 transcripts due to its different biological effect. We underlined that an in-depth knowledge of BRCA testing is mandatory for its appropriate use.
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Poly ADP ribose polymerase inhibitor
Variants of unknown significance
High grade serous ovarian cancer
Variant allele frequency
Minor allele frequency
Evidence-based network for the interpretation of germline mutant alleles
Nuclear localization signal
Single nucleotide variants
Copy number variations
Next generation sequencing
Multiplex amplification quantification
Multiplex ligation probe amplification
Tumor mutational burden
American College of Medical Genetics
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We would like to thank Franziska M. Lohmeyer for critically reviewing this manuscript.
This research received no external funding.
Confict of interest
The authors declare that they have no conficts of interest.
This study complied with the Ethical Principles for Medical Research Involving Human Subjects according to the World Medical Association Declaration of Helsinki and was certified by the Committee of the Applicable Institution of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome.
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De Paolis, E., Pietragalla, A., De Bonis, M. et al. The BRCA1 c.788G > T (NM_007294.4) variant in a high grade serous ovarian cancer (HGSOC) patient: foods for thought. Mol Biol Rep 48, 2985–2992 (2021). https://doi.org/10.1007/s11033-021-06243-x
- BRCA1/2 genes
- High grade serous ovarian cancer
- C.788G > T
- Tumor BRCA testing
- Next generation sequencing