SYSTEMS BIOLOGY TO DECIPHER CANCER-IMMUNE INTERACTIONS ACROSS SOLID PEDIATRIC AND ADULT CANCERS

Abstract

The high-throughput genomic and transcriptomic data of different cancer types are emerging and can be used to identify patient subgroups for tailored precision therapy. Various large-scale genomic studies improved our understanding of the genetic pinnings of pediatric and adult cancers. These studies, including long-non coding RNA studies, uncovered the immune subtypes of various tumors and their role in designing the treatment strategy. However, more studies are needed to understand the architecture of pediatric and adult tumors for better diagnosis and therapy. To further understand the molecular basis of pediatric and adult tumors we performed an integrative analysis of genomic and transcriptomic data. The aims of the study are to characterize the immune landscape of pediatric solid tumors, identify the druggable mutations in pediatric tumors, and deconvolute the role of dark genome matter in cancer. By analyzing the pediatric cancer transcriptomic data from the public dataset, using different immune signatures we categorized the pediatric cancer patients based on immune characteristics and identified six different distinct immune subtypes of pediatric tumors. Next, we developed an expedited pipeline that was used to reveal the genetic mutations contributing to the cancer progression and resistance to treatment in pediatric patients with solid tumors, applying this pipeline helped us to identify two mutually exclusive druggable mutations in a patient with Rhbdomyosarcom presented at Sidra Medicine. That provides us the opportunity for the development of better therapeutic options. Another interesting part of our study is characterizing the dark matter of the genome. The long non-coding RNAs are long thought to be non-functional RNAs. However, studies from the past decade showed the importance of lncRNAs in cancer and other diseases. In our study, by analyzing transcriptomic data from breast cancer we developed a three-gene signature that shows prognostic value in different cancers and could be used as a diagnostic and prognostic marker.

Date of Award	2022
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences