Targeted next generation sequencing identifies somatic mutations in a cohort of Egyptian breast cancer patients

Nassar, Auhood; Abouelhoda, Mohamed; Mansour, O.; Loutfy, Samah A.; Hafez, Mohamed M.; Gomaa, Mohammed; Bahnassy, Abeer A.; Youssef, Amira Salah El-Din; Lotfy, Mai M.; Ismail, Hoda; Ahmed, Ola; Abou-Bakr, Amany A; Zekri, Abdel-Rahman N.

doi:10.1016/j.jare.2020.04.001

Cited by 16 publications

(13 citation statements)

References 49 publications

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“…Breast cancer is the most deadly cancer among women, causing significant morbidity and mortality worldwide. 1 Currently, this disease is the most common cancer in Chinese women. 1 , 2 As with the case of all solid tumors, breast cancer is a complex disease that is difficult to treat.…”

Section: Introductionmentioning

confidence: 99%

“… 1 Currently, this disease is the most common cancer in Chinese women. 1 , 2 As with the case of all solid tumors, breast cancer is a complex disease that is difficult to treat. Breast cancer is usually classified by the presence, or absence of three receptors: estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2.…”

Section: Introductionmentioning

confidence: 99%

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Encapsulating Halofuginone Hydrobromide in TPGS Polymeric Micelles Enhances Efficacy Against Triple-Negative Breast Cancer Cells

Zuo¹,

Zhang²,

Song³

et al. 2021

IJN

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Background Halofuginone hydrobromide (HF) is a synthetic analogue of the naturally occurring quinazolinone alkaloid febrifugine, which has potential therapeutic effects against breast cancer, however, its poor water solubility greatly limits its pharmaceutical application. D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) is a water-soluble derivative of vitamin E, which can self-assemble to form polymeric micelles (PMs) for encapsulating insoluble anti-tumor drugs, thereby effectively enhancing their anti-cancer effects. Methods HF-loaded TPGS PMs (HTPMs) were manufactured using a thin-film hydration technique, followed by a series of characterizations, including the hydrodynamic diameter (HD), zeta potential (ZP), stability, drug loading (DL), encapsulation efficiency (EE), and in vitro drug release. The anti-cancer effects and potential mechanism of HTPMs were investigated in the breast cell lines MDA-MB-231 and MCF-7, and normal breast epithelial cell line Eph-ev. The breast cancer-bearing BALB/c nude mouse model was successfully established by subcutaneous injection of MDA-MB-231 cells and used to evaluate the in vivo therapeutic effect and safety of the HTPMs. Results The optimized HTPMs had an HD of 17.8±0.5 nm and ZP of 14.40±0.1 mV. These PMs exhibited DL of 12.94 ± 0.46% and EE of 90.6 ± 0.85%, along with excellent storage stability, dilution tolerance and sustained drug release in pH-dependent manner within 24 h compared to free HF. Additionally, the HTPMs had stronger inhibitory effects than free HF and paclitaxel against MDA-MB-231 triple-negative breast cancer cells, and little toxicity in normal breast epithelial Eph-ev cells. The HTPMs induced cell cycle arrest and apoptosis of MDA-MB-231 by disrupting the mitochondrial membrane potential and enhancing reactive oxygen species formation. Evaluation of in vivo anti-tumor efficacy demonstrated that HTPMs exerted a stronger tumor inhibition rate (68.17%) than free HF, and exhibited excellent biocompatibility. Conclusion The findings from this study indicate that HTPMs holds great clinical potential for treating triple-negative breast cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Encapsulating Halofuginone Hydrobromide in TPGS Polymeric Micelles Enhances Efficacy Against Triple-Negative Breast Cancer Cells

Zuo¹,

Zhang²,

Song³

et al. 2021

IJN

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“…Of interest, the TP53 drug response variant (c.215C > G) [20], was detected in more than half of our CRC group. Also, it has been recently observed in 17% of the Egyptian breast cancer patients [21]. Thus, this variant might serve as an e cient predictive marker for chemotherapy response in the Egyptian cancer patients.…”

Section: Discussionmentioning

confidence: 91%

Deep Next Generation Sequencing Identifies Somatic Mutational Signature in Egyptian Colorectal Cancer Patients

Youssef

Abdelfattah

Touny

et al. 2020

Preprint

Self Cite

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Background: Colorectal cancer (CRC) incidence is progressively increasing in Egypt. Unfortunately, there is inadequate knowledge of the acquired somatic mutations in Egyptian CRC patients which limit our understanding of its progression. To the best of our knowledge, our study is the first to sequence multiple-gene panel to identify the somatic mutation pattern associated with CRC disease progression in a cohort of Egyptian patients. Custom 72 genes, which are frequently associated with CRC, were sequenced using Qiaseq UMI-based targeted DNA panel in 120 fresh tissues classified into; inflammatory bowel disease (IBD; n=20), colonic polyp (CP; n=38) and CRC (n=62) as well as 20 biopsies with non-specific colitis served as a control group (n=20). Results: Using Ingenuity Variant Analysis (IVA), we revealed that APC, TP53 & ATM genes harbored the highly frequent CRC-specific somatic mutations (15, 11 & 6, respectively). We also identified common somatic mutations (predictors) that were associated with disease progression from colitis to CRC; APC (c.1742delA (65%)), TP53 (c.121delG (58%), c.215C>G (52%)), ATM (c.640delT (16%)), IGF2 (c.677delG (56%)), RET (c.2071G>A (37%)), ACVR2A (c.1310delA (26%)), PIK3CA (c.1173A>G (16%)) & KIT (c.1621A>C (13%)). Furthermore, pathway analysis using Ingenuity Pathway Analysis (IPA) showed that Wnt/βcatenin, ATM signaling, RTK-RAS and TGF-β were the most altered pathways in the CRC group (73%. 72%, 40% & 36%, respectively).Conclusion: In this data set, we shed the light on the most frequent somatic mutations and the most altered pathways that are crucial for understanding colorectal cancer predisposition and developing personalized therapies for the Egyptian CRC patients.

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“…Additionally, use of NGS allowed further treatment optimization and personalization, considering that the identification of specific germline or somatic mutations proved to be of predictive and prognostic value [2][3][4][5]. However, current evidence primarily stems from studies performed in Western populations, with limited data available from patients with other ethnicities or origins, like Arabs, especially for somatic mutations [6][7][8][9][10][11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Molecular Spectra and Frequency Patterns of Somatic Mutations in Arab Women with Breast Cancer

Al-Shamsi

Abu-Gheida

Abdulsamad³

et al. 2021

The Oncologist

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Background. The role of somatic mutations in breast cancer prognosis and management continues to be recognized. However, data on the molecular profiles of Arab women are limited. Materials and Methods. This was a cross-sectional study based on medical chart review of all Arab women diagnosed with breast cancer at a single institution between 2010 and 2018 who underwent next-generation sequencing with Ampliseq 46-Gene or 50-Gene. Results. A total of 78 Arab women were identified, with a median age at diagnosis of 52.3 years (range: 37-82 years; 38.5% ≤50 years). The majority of patients had stage III or IV disease (74.4%).

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Targeted next generation sequencing identifies somatic mutations in a cohort of Egyptian breast cancer patients

Cited by 16 publications

References 49 publications

Encapsulating Halofuginone Hydrobromide in TPGS Polymeric Micelles Enhances Efficacy Against Triple-Negative Breast Cancer Cells

Encapsulating Halofuginone Hydrobromide in TPGS Polymeric Micelles Enhances Efficacy Against Triple-Negative Breast Cancer Cells

Deep Next Generation Sequencing Identifies Somatic Mutational Signature in Egyptian Colorectal Cancer Patients

Molecular Spectra and Frequency Patterns of Somatic Mutations in Arab Women with Breast Cancer

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