Identification of a novel mutation in a Palestinian family with Hereditary Cancer رسالة ماجستير

Abstract

Next generation sequencing is becoming an important tool for cancer diagnosis. It presents an effective way to early detection and medical intervention to plan effective treatment that may increase the chance of survival. The purpose of this study is to utilize next generation sequencing to identify the molecular causes of breast cancer in a Palestinian family with hereditary breast cancer. We performed whole exome sequencing of DNA extracted from the blood of two sisters diagnosed with breast cancer and validates the results by sanger sequencing. We used segregation analysis to confirm the presence of the identified variant in the daughters of the targeted family members. Our analysis resulted in the identification of a novel stop-gain mutation IGSF8 c.C487T: p.R163X, which is located in exon 3 and may lead to unfunctional protein. This was subsequently validated by sanger sequencing. Furthermore, segregation analysis confirmed the presence of this variant in the daughters of the targeted family members. Our study shows that WES provides a more conclusive genetics diagnoses compared to panel sequencing. It also confirms that molecular studies and NGS applications are needed to detect significant breast cancer relevant mutations, which may in return lead to the right medical interventions.