Virginia Research Day 2022

Faculty Research Biomedical

02 Characterizing Mutations In Tumor Infiltrating Leukocytes In Non-Small Cell Lung Cancer Using Single-Cell RNA Sequencing Data

Ramu Anandakrishnan; Ian Zyvoloski; Lucas Zyvoloski Corresponding Author: ramu@vt.edu

VCOM Virginia Severna Park Middle School, Maryland

The immune system plays a critical role in inhibiting tumor growth. Mutations acquired by tumor cells that prevent immune destruction have been extensively studied. In addition, the clonal hematopoietic accumulation of mutations in immune cells have been implicated in myeloid leukemia. However, the potential role of mutations in tumor infiltrating leukocytes (TIL) in the progression of solid cancers has not been previously investigated. In this study we analyzed single-cell RNA sequencing (scRNA-seq) data from 21 non-small cell lung cancer (NSCLC) tumor samples, to identify and characterize mutations in TIL. An estimated 78% (59-96%) of the 63,174 cells from these samples were classified as leukocytes based on their gene expression profile. Despite the limitations of calling variants using scRNA-seq data, we identified a total of 132,495 variants in leukocytes, 72,191 (56%) of which were protein altering variants. Of these protein altering variants, we identified over 500 rare, clonally-expanded, leukocyte-only variant, representing potential pathogenic mutations in TIL. All of these variants occurred in genes associated with immune system pathways. Further experimental investigation is required to determine if these mutations affect immune system activity, potentially affecting the progression of tumor growth.

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