Cancer Genomics
 

Identifying Genomic Variants in Large-Scale Cancer Cohort
  Cancer genomics focused on characterizing genomic alterations such as point mutations, copy number variations and structural alterations in cancers are enabled through usage of next-generation sequencing technologies. The study of cancer genomes identified aberrations in genomes that drive development and growth of various cancer (Vogelstein et al., Science 2018). In the vast areas of genomics, we focus on processing high quality whole genome sequencing data and identifying cancer related genes and target noncoding regional mutations that can give tumors growth advantage. The characterization of genomic alteration enables categorizing patients and identifying possible prognostic, diagnostic and predictive biomarker targets. (Collins et al., Trends in Pharm. Sci. 2017) Despite the advanced efforts to understand cancer genome, various tumoral pathways contributing to heterogeneity of cancer and direct relationship of genomic alterations to clinical data could not be easily detected. The integrative analyses of multi-omics such as transcriptomes and epigenome data (methylation) enables the identification of more comprehensive alterations in cancer genome and its consequences of alterations being depicted in other omics data (Woo et al., Nat comm 2017).

Structural Variation in Cancer Genome
  Structural variations(SVs) are genetic alterations that affect more than 50 base pairs in the genome and the types of SVs include insertions, deletions, inversions and translocations relative to the reference genome (Alkan et al, Nat. Rev. Gen. 2011). SVs contribute to human genetic and phenotypic diversity and play causal roles in many Mendelian and complex diseases, including cancers (Stankiewicz and Lupski, Annu Rev Med 2010). The integration of Hepatitis B (HBV) genomes into human genomes are thought to be early events in hepatocellular carcinogenesis and shown to recurrently affect TERT gene promoter with correlated dysregulation (Fujimoto et al, Nat. Gen. 2016). Chromosomal instability, characterized by extensive copy number variations, is also a major driver of cancers including colorectal cancers. Therefore, we are analyzing structural variation in cancers using massive parallel sequencing of cancer genomes to find genetic biomarkers for cancer diagnosis and prognosis and to uncover underlying mechanisms of carcinogenesis.

  There have been a lot of advances in the area of structural variations with the short-read sequencing during the decade since the invention of SBS(seqeuncing-by-synthesis) technology. However, due to its short read lengths, the analysis of repetitive regions and complex SVs are still limited and the haplotype phasing requires trio design or large scale genome projects. The third generation sequencing technology provided by Pacific Bioscience or Oxford Nanopore Technology(ONT) have made it possible to overcome those issues through theirs long read lengths attained by single-molecule sequencing methods( F. J. Sedlazeck et al, Nat. Gen. 2018 ). Based on ONT nanopore sequencing, we are aiming to achieve the personal genomic profiling and get the comprehensive landscape of complex structural variations in cancer genome.

Validation of Cell-free DNA mutations by Targeted Next Generation Sequencing
  DNA isolated from tumor biopsy tissue has been widely studied to characterize cancer traits and has contributed to cancer research. Since almost a decade ago, cell-free DNA (cfDNA) isolated from plasma of cancer patients’ blood samples has been getting the limelight as non-invasive liquid biopsy samples. cfDNA is secreted from cells through apoptosis and necrosis, circulating in the bloodstream and various body fluids. These days, several important facts have been discovered as follows: (Wan et al., Nat Rev Cancer, 2017)


• The quantity of cfDNA from the normal individuals and tumor patients are different. The plasma of tumor patients contains much more cfDNA than that of the normal people does. In addition, the quantity of cfDNA in plasma differs according to the stages of the tumor and before and after the surgery.


• Genetic and epigenetic modification of the genome of primary and metastasized tumor can be retained in the genome of cfDNA molecules.


  Targeted sequencing is a useful method to target a lot of genomic regions of interest simultaneously to profile genetic variations in cancer samples. Furthermore, targeted sequencing can be adapted to various sequencing platforms - not only next-generation sequencing platforms that generate bulk sequencing data such as Illumina and Ion Torrent® and Oxford Nanopore® sequencing, but also single-cell sequencing platforms. By the detection of genomic alterations of cfDNA and genomic DNA, we are expecting to develop novel prognostic and predictive markers to forecast the survival rates, responses of the patients after the treatment of immunotherapies, chemotherapies and the radiation therapies.