School of Science Division of Life Science 24 Human Complex Disease Genomics and Bioinformatics Supervisor: LIANG Chun / LIFS Co-supervisor: XUE Hong / LIFS Student: NG Wai Ching / BIOT-AB Course: UROP 1000, Summer Brain metastases, which account for over half of all diagnosed brain tumors and affect 10–30% of adults with systemic cancer, are associated with extremely poor prognosis and limited treatment options. While genetic mutations in key oncogenes and tumor suppressors are established drivers of brain tumorigenesis, the contribution of Alu retrotransposons, which are mobile genetic elements capable of inducing genomic instability, remains largely unexplored. This study aims to investigate the involvement of Alu elements in the molecular pathology of brain metastases by identifying somatic Alu insertions. We employed whole genome sequencing (NGS) and inter-Alu PCR to analyze metastatic brain tumor tissues and matched normal white blood cells (germline controls) from six Chinese patients. By characterizing the landscape of Alu insertions in brain metastases, this research seeks to provide new insights into the mechanisms of tumor evolution and identify novel molecular features that could inform future therapeutic strategies. Human Complex Disease Genomics and Bioinformatics Supervisor: LIANG Chun / LIFS Co-supervisor: XUE Hong / LIFS Student: TASNEEM Maisha / BIOT Course: UROP 1100, Spring UROP 2100, Summer This study analyzes copy number variation (CNV) dynamics in 26 lung primaries and 33 brain metastases patients across cell cycle phases (G1b, S1, S2, S3, S4, G2), using Loss/Gain ratios and CNV gain/loss metrics. Early phases (G1b, S1) show balanced ratios, while metastases exhibit higher losses in S2 (450kb, p=0.037) and gains in G1b/S1. Primaries display elevated losses in S4/G2 (e.g., G2 300kb, p=0.009). These windowsize-dependent patterns, visualized via scatterplots, suggest metastatic adaptation through gain-driven proliferation and loss-mediated tumor suppressor inactivation. Low G2 Loss/Gain ratios in metastases, reflecting reduced losses, can potentially emerge as a predictive marker for brain metastasis risk in Non Small Cell Lung Cancer (NSCLC) primaries. These findings advocate phase-aware biomarkers to improve early detection and personalized medical interventions.
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