Abstract
BackgroundBreast cancer (BC) is the 2nd most prevalent malignancy worldwide and is the most prevalent cancer among Egyptian women. The number of newly described cancer-associated genes has grown exponentially since the emergence of next-generation sequencing (NGS) technology. We aim to identify activating mutations in liquid biopsy of Egyptian breast cancer patients using targeted NGS technology. We also demonstrate the microsatellite instability (MSI) status using BAT25, BAT26, and NR27 markers which are tested on the Bioanalyzer 2100 system.ResultsTwenty-one variants were detected in 15 genes: 7 Substitution-Missense, 12 Substitution-coding silent, and 2 Substitution-intronic. Regarding ClinVar database, out of 21 variants there were 14 benign variants, 3 variants with conflicting interpretations of pathogenicity, 3 variants not reported, and 1 drug response variant. TP53 p.(Pro72Arg) missense mutations were found in 75% of patients. PIK3CA p.(Ile391Met), KDR p.(Gln472His) missense mutations were detected in 25% of patients each. Two patients revealed APC gene missense mutation with p.(Ile1307Lys) and p.(Glu1317Gln) variants. Only one patient showed ATM p.(Phe858Leu) gene mutation and one showed FGFR3 p.(Ala719Thr) variant. Regarding microsatellite instability (MSI) status, 2/8 (25%) patients were MSS, 3/8 (37.5%) patients were MSI-L, and 3/8 (37.5%) patients were MSI-HI.ConclusionIt is essential to use and validate minimally invasive liquid biopsy for activating mutations detection by next-generation sequencing especially in patients with inoperable disease or bone metastasis. This work should be extended with larger patient series with comparison of genetic mutations in liquid-based versus tissue-based biopsy and longer follow up period.
Highlights
Breast cancer (BC) is the 2nd most prevalent malignancy worldwide and is the most prevalent cancer among Egyptian women
We demonstrate the microsatellite instability (MSI) status using BAT25, BAT26, and NR27 markers which are tested on the Bioanalyzer 2100 system
Acquired variant is present with a lower variant allele frequency (VAF) as it is not found in all cells
Summary
Breast cancer (BC) is the 2nd most prevalent malignancy worldwide and is the most prevalent cancer among Egyptian women. The single available substance for molecular testing was the patient’s formalin-fixed paraffinembedded (FFPE) tumor tissue. This FFPE samples have many advantages as it is accessible material, simple for usage and storage. FFPE material has obvious disadvantages, such as inability to acquire in cases of inoperable tumors and bone metastases with some difficulties to capture the tumor’s heterogeneity. This genetic material collected as a result of paraffin processing of tissue, is commonly of low/poor quality, and not adequate for molecular profiling [8]. The most essential point that the molecular profile of cancer is transformed, basically after targeted therapy and these alternations cannot be noticed by testing the 1ry tumor material but require invasive tissue rebiopsies [9]
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