BRAF V600E mutation associated with papillary high-grade serous ovarian cystadenocarcinoma in a 22q11.2DS patient

Objective: Ovarian cancers exhibit very heterogeneous genetic and genomic aberrations with various pathogenetic and prognostic values. Chromosome 22 abnormalities, including del(22q) and duplications, are genetic multisystemic disorders, most commonly affecting cardiovascular, immune, and gastrointe...

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Main Authors: Maria Antonietta Castaldi, Nadia Petrillo, Carmine Selleri, Monica Ianniello, Anna Maria Della Corte, Eloisa Evangelista, Luigia De Falco, Roberto Sirica, Marika Casillo, Alessia Caleo, Alessandro Caputo, Pio Zeppa, Salvatore Giovanni Castaldi, Pasqualina Scala, Bianca Serio, Giovanni Savarese, Valentina Giudice
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Gynecologic Oncology Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352578925001018
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author Maria Antonietta Castaldi
Nadia Petrillo
Carmine Selleri
Monica Ianniello
Anna Maria Della Corte
Eloisa Evangelista
Luigia De Falco
Roberto Sirica
Marika Casillo
Alessia Caleo
Alessandro Caputo
Pio Zeppa
Salvatore Giovanni Castaldi
Pasqualina Scala
Bianca Serio
Giovanni Savarese
Valentina Giudice
author_facet Maria Antonietta Castaldi
Nadia Petrillo
Carmine Selleri
Monica Ianniello
Anna Maria Della Corte
Eloisa Evangelista
Luigia De Falco
Roberto Sirica
Marika Casillo
Alessia Caleo
Alessandro Caputo
Pio Zeppa
Salvatore Giovanni Castaldi
Pasqualina Scala
Bianca Serio
Giovanni Savarese
Valentina Giudice
author_sort Maria Antonietta Castaldi
collection DOAJ
description Objective: Ovarian cancers exhibit very heterogeneous genetic and genomic aberrations with various pathogenetic and prognostic values. Chromosome 22 abnormalities, including del(22q) and duplications, are genetic multisystemic disorders, most commonly affecting cardiovascular, immune, and gastrointestinal systems, while tumors are rarely reported. Methods: In this case report, we described a patient with 22q11.2 deletion syndrome who developed a papillary high-grade serous ovarian cystadenocarcinoma, and targeted- and whole-exome sequencing for genomic alterations identification and RNA-sequencing for transcriptomics analysis were performed. Results: Whole exome sequencing identified a B-Raf proto-oncogene, Serine/Threonine kinase (BRAF) V600E mutation, along with other somatic mutations, including BARD1 missense variant. Constitutional activation of the BRAF protein and its tumorigenic role in our patient was confirmed by upregulation of its downstream KRAS signaling pathway in tumor tissue compared to circulating cells. Conclusion: BRAF pathways could be involved in the molecular biology of papillary high-grade serous ovarian cystadenocarcinoma in a setting of 22q11.2 deletion syndrome.
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spelling doaj-art-efafd7425436451ca6cc69a5e6e67c112025-08-20T02:10:02ZengElsevierGynecologic Oncology Reports2352-57892025-06-015910177610.1016/j.gore.2025.101776BRAF V600E mutation associated with papillary high-grade serous ovarian cystadenocarcinoma in a 22q11.2DS patientMaria Antonietta Castaldi0Nadia Petrillo1Carmine Selleri2Monica Ianniello3Anna Maria Della Corte4Eloisa Evangelista5Luigia De Falco6Roberto Sirica7Marika Casillo8Alessia Caleo9Alessandro Caputo10Pio Zeppa11Salvatore Giovanni Castaldi12Pasqualina Scala13Bianca Serio14Giovanni Savarese15Valentina Giudice16High Risk Pregnancy Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, Italy; Department of Medicine, Surgery, and Dentistry, University of Salerno, 84081 Baronissi, ItalyAmes Center s.r.l, Casalnuovo di Naples, Naples, ItalyDepartment of Medicine, Surgery, and Dentistry, University of Salerno, 84081 Baronissi, Italy; Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, Italy; Corresponding authors at: Department of Medicine, Surgery, and Dentistry, University of Salerno, 84081 Baronissi, Italy.Ames Center s.r.l, Casalnuovo di Naples, Naples, ItalyHematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, ItalyAmes Center s.r.l, Casalnuovo di Naples, Naples, ItalyAmes Center s.r.l, Casalnuovo di Naples, Naples, ItalyAmes Center s.r.l, Casalnuovo di Naples, Naples, ItalyAmes Center s.r.l, Casalnuovo di Naples, Naples, ItalyAnatomy Pathology, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, ItalyAnatomy Pathology, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, ItalyAnatomy Pathology, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, ItalyDepartment of Medicine, Surgery, and Dentistry, University of Salerno, 84081 Baronissi, ItalyDepartment of Medicine, Surgery, and Dentistry, University of Salerno, 84081 Baronissi, Italy; Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, ItalyHematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, ItalyAmes Center s.r.l, Casalnuovo di Naples, Naples, ItalyDepartment of Medicine, Surgery, and Dentistry, University of Salerno, 84081 Baronissi, Italy; Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, 84131 Salerno, Italy; Corresponding authors at: Department of Medicine, Surgery, and Dentistry, University of Salerno, 84081 Baronissi, Italy.Objective: Ovarian cancers exhibit very heterogeneous genetic and genomic aberrations with various pathogenetic and prognostic values. Chromosome 22 abnormalities, including del(22q) and duplications, are genetic multisystemic disorders, most commonly affecting cardiovascular, immune, and gastrointestinal systems, while tumors are rarely reported. Methods: In this case report, we described a patient with 22q11.2 deletion syndrome who developed a papillary high-grade serous ovarian cystadenocarcinoma, and targeted- and whole-exome sequencing for genomic alterations identification and RNA-sequencing for transcriptomics analysis were performed. Results: Whole exome sequencing identified a B-Raf proto-oncogene, Serine/Threonine kinase (BRAF) V600E mutation, along with other somatic mutations, including BARD1 missense variant. Constitutional activation of the BRAF protein and its tumorigenic role in our patient was confirmed by upregulation of its downstream KRAS signaling pathway in tumor tissue compared to circulating cells. Conclusion: BRAF pathways could be involved in the molecular biology of papillary high-grade serous ovarian cystadenocarcinoma in a setting of 22q11.2 deletion syndrome.http://www.sciencedirect.com/science/article/pii/S2352578925001018DiGeorge syndromeBRAFOvarian tumor
spellingShingle Maria Antonietta Castaldi
Nadia Petrillo
Carmine Selleri
Monica Ianniello
Anna Maria Della Corte
Eloisa Evangelista
Luigia De Falco
Roberto Sirica
Marika Casillo
Alessia Caleo
Alessandro Caputo
Pio Zeppa
Salvatore Giovanni Castaldi
Pasqualina Scala
Bianca Serio
Giovanni Savarese
Valentina Giudice
BRAF V600E mutation associated with papillary high-grade serous ovarian cystadenocarcinoma in a 22q11.2DS patient
Gynecologic Oncology Reports
DiGeorge syndrome
BRAF
Ovarian tumor
title BRAF V600E mutation associated with papillary high-grade serous ovarian cystadenocarcinoma in a 22q11.2DS patient
title_full BRAF V600E mutation associated with papillary high-grade serous ovarian cystadenocarcinoma in a 22q11.2DS patient
title_fullStr BRAF V600E mutation associated with papillary high-grade serous ovarian cystadenocarcinoma in a 22q11.2DS patient
title_full_unstemmed BRAF V600E mutation associated with papillary high-grade serous ovarian cystadenocarcinoma in a 22q11.2DS patient
title_short BRAF V600E mutation associated with papillary high-grade serous ovarian cystadenocarcinoma in a 22q11.2DS patient
title_sort braf v600e mutation associated with papillary high grade serous ovarian cystadenocarcinoma in a 22q11 2ds patient
topic DiGeorge syndrome
BRAF
Ovarian tumor
url http://www.sciencedirect.com/science/article/pii/S2352578925001018
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