Identification of gene mutations involved in drug resistance in liver cancer using RNA-Seq data analysis

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Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Enformatik Enstitüsü, Sağlık Bilişimi Anabilim Dalı, Türkiye

Tezin Onay Tarihi: 2016

Öğrenci: MONA SHOJAEI

Eş Danışman: RENGÜL ATALAY, AYBAR CAN ACAR

Özet:

A significant concern in cancer research is the detection of cancer associated somatic mutations. Liver cancer is the 5th most common and 2nd deadliest cancer in the world. Several somatic mutations were previously reported in liver cancer but their relations to chemotherapeutic response was not studied in detail. In this study, the relationship between mutation status and drug treatment response of well-differentiated Huh7 and poorly-differentiated Mahlavu liver cancer cells were analyzed. The RNA-Seq data of each cancer cell line (as control) was compared to “sorafenib” and “PI3K/Akt Pathway inhibitors” treated data. Somatic mutations associated with drug resistance were comparatively identified with MuTect tool. The results were then filtered to distinguish the missense mutations. The common genes among drug-resistant sets were found to be associated with liver cancer perseverance and aggressiveness. SLC39A5, FRG1, PPHLN1 and SRP9 gene mutations were found to be the most significant, shared among three drug treated sets. The sets were further investigated in detail to discover the liver cancer associated survival genes. Using our results, appropriate targets can be defined that play critical roles in cancerous cell growth for drug development purposes.