Accès ouvert

Genetic mutations in HER2-positive breast cancer: possible association with response to trastuzumab therapy

Article scientifique 2023 Anglais

Résumé

BACKGROUND: HER2-positive breast cancer occurs in 15-20% of breast cancer patients and is characterized by poor prognosis. Trastuzumab is considered the key drug for treatment of HER2-positive breast cancer patients. It improves patient survival; however, resistance to trastuzumab remains a challenge in HER2-positive breast cancer patients. Therefore, the prediction of response to trastuzumab is crucial to choose optimal treatment regimens. The aim of the study was to identify genetic variants that could predict response to anti-HER2-targeted therapy (trastuzumab) using next-generation sequencing. METHOD: Genetic variants in the hotspot regions of 17 genes were studied in 24 Formalin-Fixed Paraffin-Embedded (FFPE) samples using Ion S5 next-generation sequencing system. FFPE samples were collected from HER2‑positive breast cancer patients previously treated with anti‑HER2‑targeted treatment (Trastuzumab). Patients were divided into two groups; trastuzumab-sensitive group and trastuzumab-resistant group based on their response to targeted therapy. RESULTS: We identified 29 genetic variants in nine genes that only occurred in trastuzumab-resistant patients and could be associated with resistance to targeted therapy including TP53, ATM, RB1, MLH1, SMARCB1, SMO, GNAS, CDH1, and VHL. Four variants out of these 29 variants were repeated in more than one patient; two variants in TP53, one variant in ATM gene, and the last variant in RB1 gene. In addition, three genes were found to be mutated only in resistant patients; MLH1, SMARCB1 and SMO genes. Moreover, one novel allele (c.407A > G, p. Gln136Arg) was detected within exon 4 of TP53 gene in one resistant patient. CONCLUSION: NGS sequencing is a useful tool to detect genetic variants that could predict response to trastuzumab therapy.

Citer ce document

Zakaria, N., Hashad, D., Saied, M., Hegazy, N., Elkayal, A., Tayae, E. (2023). Genetic mutations in HER2-positive breast cancer: possible association with response to trastuzumab therapy. https://doi.org/10.1186/s40246-023-00493-5

Accès au document

Texte intégral en lecture en ligne, réservé aux abonnés SPHAERO et aux membres de l'institution. Se connecter

Voir l'article sur le site de la revue

Auteur(s)

Nermine H. Zakaria Doaa Ibrahim Hashad Marwa H. Saied Neamat Hegazy Alyaa Elkayal Eman Tayae

Statistiques

Consultations : 2

Téléchargements : 0