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The BRCA1 c.788G > T (NM_007294.4) variant in a high grade serous ovarian cancer (HGSOC) patient: foods for thought

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Abstract

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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Fig. 1

Figure source: https://varsome.com/

Fig. 2

Source: Amplicon Suite software (SmartSeq, Novara, Italy)

Abbreviations

BRCA:

BRCA1/2

BC:

Breast cancer

OC:

Ovarian cancer

PVs:

Pathogenic variants

PARPi:

Poly ADP ribose polymerase inhibitor

VUSs:

Variants of unknown significance

HGSOC:

High grade serous ovarian cancer

tBRCA:

Tumor BRCA

VAF:

Variant allele frequency

MAF:

Minor allele frequency

F1CDx:

FoundationOne®CDx

BRCA1-FL:

BRCA1 full-length

ENIGMA:

Evidence-based network for the interpretation of germline mutant alleles

NLS:

Nuclear localization signal

gBRCA:

Germline BRCA

SNPs:

Single nucleotide variants

CNVs:

Copy number variations

NGS:

Next generation sequencing

MAQ:

Multiplex amplification quantification

MLPA:

Multiplex ligation probe amplification

MSI:

Microsatellite instability

TMB:

Tumor mutational burden

ACMG:

American College of Medical Genetics

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Acknowledgements

We would like to thank Franziska M. Lohmeyer for critically reviewing this manuscript.

Funding

This research received no external funding.

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Authors and Affiliations

  1. Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Elisa De Paolis, Maria De Bonis, Andrea Urbani & Angelo Minucci

  2. Division of Gynecologic Oncology, Department of Women’s and Children’s Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Antonella Pietragalla, Anna Fagotti & Giovanni Scambia

  3. Catholic University of the Sacred Heart, Rome, Italy

    Anna Fagotti, Andrea Urbani & Giovanni Scambia

Authors
  1. Elisa De Paolis
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  2. Antonella Pietragalla
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  3. Maria De Bonis
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  4. Anna Fagotti
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  5. Andrea Urbani
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  6. Giovanni Scambia
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  7. Angelo Minucci
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Contributions

EDP and AM conceived the project and wrote the paper; EDP and MDB performed the experiments and analysed the data; AU contributed to analyses and interpretation of data; AP, AF and GS contributed to patient selection and clinical evaluation. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Angelo Minucci.

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Confict of interest

The authors declare that they have no conficts of interest.

Ethical approval

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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Written informed consent was obtained from the patient included in this study.

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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

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  • DOI: https://doi.org/10.1007/s11033-021-06243-x

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