Abstract
Objective
Universal genetic testing has become increasingly important in the management of epithelial
tubo-ovarian and peritoneal carcinoma. Worldwide, reported incidences of deleterious
BRCA mutations vary between 12% and 15%. We sought to evaluate the incidence in our population,
given its specific genetic background (French-Canadian ancestry).
Method
Mainstream genetic testing was implemented in our service in May 2017 and offered
to all patients with epithelial tubo-ovarian or peritoneal carcinomas, except mucinous
and borderline tumours. Data were prospectively collected in a database and retrospectively
analyzed.
Results
We tested 222 patients in our centre, of whom 183 (82.4%) had high-grade serous carcinoma
(HGSC). Overall, 139 patients had no identified mutation (62.6%). Deleterious BRCA1 and BRCA2 mutations were found in 12 patients (5.4%): 6 had BRCA1, and 6 BRCA2 mutations; 11 of these patients had HGSC. Other non–BRCA mutations (ATM, RAD51C, RAD51D, BRIP1, CDH1, MRE11, MSH6, MUTYH, PALB2, and PMS2) were observed in an additional 20 patients (9.0%), of whom 18 had HGSC. A total
of 63 different variants of unknown significance (VUS) were found, of which 4 were
in the BRCA1 and BRCA2 genes. Deleterious mutations were not identified in clear cell carcinomas, and only
1 was found in low-grade serous carcinoma.
Conclusion
In our French-Canadian population, the incidence of deleterious germline BRCA mutations was surprisingly low at 5.4%—less than half that reported in the literature.
This may affect patient response to poly (ADP-ribose) polymerase (PARP) inhibitor
(PARPi) therapy. Mainstream genetic testing was successfully implemented in our service
and facilitated access to genetic testing in our patient population.
Résumé
Objectif
Les tests génétiques systématiques prennent de plus en plus d’importance dans la prise
en charge du carcinome épithélial tubo-ovarien ou péritonéal. À l’échelle mondiale,
la fréquence déclarée des mutations délétères des gènes BRCA varie entre 12 et 15 %. Nous avons cherché à évaluer la fréquence dans notre population,
étant donné son origine génétique particulière (ascendance canadienne-française).
Méthodologie
Les tests génétiques grand public ont été mis en œuvre dans notre service en mai 2017
et offerts à toutes les patientes atteintes d’un carcinome épithélial tubo-ovarien
ou péritonéal, à l’exception des tumeurs mucineuses ou à la limite de la malignité.
Les données ont été recueillies prospectivement dans une base de données et analysées
rétrospectivement.
Résultats
Nous avons évalué 222 patientes dans notre centre, dont 183 (82,4 %) présentaient
un carcinome séreux de haut grade (CSHG). Dans l’ensemble, 139 patientes n’avaient
aucune mutation (62,6 %). Une mutation délétère des gènes BRCA1 et BRCA2 a été détectée chez 12 patientes (5,4 %). Parmi ces patientes, 6 avaient une mutation
du gène BRCA1, et 6 avaient une mutation du gène BRCA2; 11 patientes présentaient un CSHG. Une mutation de gènes autres que les BRCA (ATM, RAD51C, RAD51D, BRIP1, CDH1, MRE11, MSH6, MUTYH, PALB2 et PMS2) a été observée chez 20 autres patientes (9,0 %), dont 18 avaient un CSHG. Au total,
63 variants de signification inconnue (VSI) ont été détectés, dont 4 se trouvaient
dans les gènes BRCA1 et BRCA2. Aucune mutation délétère n’a été détectée dans les cas de carcinomes à cellules
claires, et 1 seule a été observée dans un cas de carcinome séreux de bas grade.
Conclusion
Dans notre population canadienne-française, la fréquence des mutations germinales
délétères des gènes BRCA était étonnamment faible, soit 5,4 %, ce qui correspond à moins de la moitié de la
fréquence rapportée dans la littérature. Cette constatation pourrait influer sur la
réponse des patientes au traitement par inhibiteurs de poly-ADP-ribose polymérase
(PARP). Les tests génétiques grand public ont été mis en œuvre avec succès dans notre
service et ont facilité l’accès aux tests génétiques dans notre population de patientes.
Keywords
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Article info
Publication history
Published online: June 29, 2022
Accepted:
June 1,
2022
Received:
February 21,
2022
Footnotes
Disclosures: The authors declare they have nothing to disclose.
All authors have indicated they meet the journal’s requirements for authorship.
Identification
Copyright
© 2022 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.
