التفاصيل البيبلوغرافية
| العنوان: |
In Silico Prediction of BRCA1 and BRCA2 Variants with Conflicting Clinical Interpretation in a Cohort of Breast Cancer Patients. |
| المؤلفون: |
Stella, Stefania, Vitale, Silvia Rita, Massimino, Michele, Martorana, Federica, Tornabene, Irene, Tomarchio, Cristina, Drago, Melissa, Pavone, Giuliana, Gorgone, Cristina, Barone, Chiara, Bianca, Sebastiano, Manzella, Livia |
| المصدر: |
Genes; Jul2024, Vol. 15 Issue 7, p943, 15p |
| مستخلص: |
Germline BRCA1/2 alteration has been linked to an increased risk of hereditary breast and ovarian cancer syndromes. As a result, genetic testing, based on NGS, allows us to identify a high number of variants of uncertain significance (VUS) or conflicting interpretation of pathogenicity (CIP) variants. The identification of CIP/VUS is often considered inconclusive and clinically not actionable for the patients' and unaffected carriers' management. In this context, their assessment and classification remain a significant challenge. The aim of the study was to investigate whether the in silico prediction tools (PolyPhen-2, SIFT, Mutation Taster and PROVEAN) could predict the potential clinical impact and significance of BRCA1/2 CIP/VUS alterations, eventually impacting the clinical management of Breast Cancer subjects. In a cohort of 860 BC patients, 10.6% harbored BRCA1 or BRCA2 CIP/VUS alterations, mostly observed in BRCA2 sequences (85%). Among them, forty-two out of fifty-five alterations were predicted as damaging, with at least one in silico that used tools. Prediction agreement of the four tools was achieved in 45.5% of patients. Moreover, the highest consensus was obtained in twelve out of forty-two (28.6%) mutations by considering three out of four in silico algorithms. The use of prediction tools may help to identify variants with a potentially damaging effect. The lack of substantial agreement between the different algorithms suggests that the bioinformatic approaches should be combined with the personal and family history of the cancer patients. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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