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Article

Clinical Impact of Next-Generation Sequencing Multi-Gene Panel Highlighting the Landscape of Germline Alterations in Ovarian Cancer Patients

1
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
2
Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
3
Biostatistics and Clinical Trials Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
4
Oncology Department, Santa Maria Delle Croci Hospital, 48121 Ravenna, Italy
5
Department of Obstetrics and Gynaecology, AUSL Romagna, Santa Maria Delle Croci Hospital, 48121 Ravenna, Italy
6
Romagna Cancer Registry, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
7
Department of Oncology, Ospedale Infermi, 47923 Rimini, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2022, 23(24), 15789; https://doi.org/10.3390/ijms232415789
Submission received: 18 October 2022 / Revised: 1 December 2022 / Accepted: 8 December 2022 / Published: 13 December 2022

Abstract

BRCA1 and BRCA2 are the most frequently mutated genes in ovarian cancer (OC) crucial both for the identification of cancer predisposition and therapeutic choices. However, germline variants in other genes could be involved in OC susceptibility. We characterized OC patients to detect mutations in genes other than BRCA1/2 that could be associated with a high risk of developing OC and permit patients to enter the most appropriate treatment and surveillance program. Next-generation sequencing analysis with a 94-gene panel was performed on germline DNA of 219 OC patients. We identified 34 pathogenic/likely pathogenic variants in BRCA1/2 and 38 in other 21 genes. The patients with pathogenic/likely pathogenic variants in the non-BRCA1/2 genes mainly developed OC alone compared to the other groups that also developed breast cancer or other tumors (p = 0.001). Clinical correlation analysis showed that the low-risk patients were significantly associated with platinum sensitivity (p < 0.001). Regarding PARP inhibitors (PARPi) response, the patients with pathogenic mutations in the non-BRCA1/2 genes had worse PFS and OS. Moreover, a statistically significantly worse PFS was found for every increase of one thousand platelets before PARPi treatment. To conclude, knowledge about molecular alterations in genes beyond BRCA1/2 in OC could allow for more personalized diagnostic, predictive, prognostic, and therapeutic strategies for OC patients.
Keywords: ovarian cancer; BRCA1/2; cancer predisposition; platinum sensitivity; PARP inhibitors; platelets ovarian cancer; BRCA1/2; cancer predisposition; platinum sensitivity; PARP inhibitors; platelets

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MDPI and ACS Style

Gurioli, G.; Tedaldi, G.; Farolfi, A.; Petracci, E.; Casanova, C.; Comerci, G.; Danesi, R.; Arcangeli, V.; Ravegnani, M.; Calistri, D.; et al. Clinical Impact of Next-Generation Sequencing Multi-Gene Panel Highlighting the Landscape of Germline Alterations in Ovarian Cancer Patients. Int. J. Mol. Sci. 2022, 23, 15789. https://doi.org/10.3390/ijms232415789

AMA Style

Gurioli G, Tedaldi G, Farolfi A, Petracci E, Casanova C, Comerci G, Danesi R, Arcangeli V, Ravegnani M, Calistri D, et al. Clinical Impact of Next-Generation Sequencing Multi-Gene Panel Highlighting the Landscape of Germline Alterations in Ovarian Cancer Patients. International Journal of Molecular Sciences. 2022; 23(24):15789. https://doi.org/10.3390/ijms232415789

Chicago/Turabian Style

Gurioli, Giorgia, Gianluca Tedaldi, Alberto Farolfi, Elisabetta Petracci, Claudia Casanova, Giuseppe Comerci, Rita Danesi, Valentina Arcangeli, Mila Ravegnani, Daniele Calistri, and et al. 2022. "Clinical Impact of Next-Generation Sequencing Multi-Gene Panel Highlighting the Landscape of Germline Alterations in Ovarian Cancer Patients" International Journal of Molecular Sciences 23, no. 24: 15789. https://doi.org/10.3390/ijms232415789

APA Style

Gurioli, G., Tedaldi, G., Farolfi, A., Petracci, E., Casanova, C., Comerci, G., Danesi, R., Arcangeli, V., Ravegnani, M., Calistri, D., Zampiga, V., Cangini, I., Fonzi, E., Virga, A., Tassinari, D., Rosati, M., Ulivi, P., & De Giorgi, U. (2022). Clinical Impact of Next-Generation Sequencing Multi-Gene Panel Highlighting the Landscape of Germline Alterations in Ovarian Cancer Patients. International Journal of Molecular Sciences, 23(24), 15789. https://doi.org/10.3390/ijms232415789

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