Neemat Kassem1, Hebatallah Kassem2, Loay Kassem3, Mohamed Hassan3. 1. Clinical and Chemical Pathology Department, Kasr Al Ainy Centre of Clinical Oncology & Nuclear Medicine, School of Medicine, Cairo University, Cairo, Egypt. 2. Clinical and Chemical Pathology Department, Kasr Al Ainy Centre of Clinical Oncology & Nuclear Medicine, School of Medicine, Cairo University, Cairo, Egypt. Heba.kasem@hotmail.com. 3. Clinical Oncology Department, School of Medicine, Cairo University, Cairo, Egypt.
Abstract
BACKGROUND: Breast 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. RESULTS: Twenty-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. CONCLUSION: It 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.
BACKGROUND:Breast 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 cancerpatients 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. RESULTS: Twenty-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. CONCLUSION: It 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.
Entities:
Keywords:
Activating mutations; Breast cancer; Microsatellite instability; Next-generation sequencing
Authors: Michael J Bamshad; Sarah B Ng; Abigail W Bigham; Holly K Tabor; Mary J Emond; Deborah A Nickerson; Jay Shendure Journal: Nat Rev Genet Date: 2011-09-27 Impact factor: 53.242
Authors: Bert Vogelstein; Nickolas Papadopoulos; Victor E Velculescu; Shibin Zhou; Luis A Diaz; Kenneth W Kinzler Journal: Science Date: 2013-03-29 Impact factor: 47.728
Authors: C Dilara Savci-Heijink; Hans Halfwerk; Gerrit K J Hooijer; Hugo M Horlings; Jelle Wesseling; Marc J van de Vijver Journal: Breast Cancer Res Treat Date: 2015-03-29 Impact factor: 4.872
Authors: Neemat M Kassem; Wael S Makar; Hebatallah A Kassem; Soha Talima; Mustafa Tarek; Hadeer Hesham; Mohamed A El-Desouky Journal: Asian Pac J Cancer Prev Date: 2019-09-01