Abstract

Abstract Distinct genomic signature of a patient's cancer could provide a clue to design and predict accurate therapeutic responses to targeted medicine. Current approaches regarding heterogeneous cancer cells en masse as a pooled population, however, hardly reflect complete genomic landscape of tumor diversity, missing potentially important minor clones' implications regarding metastasis and drug resistance. Here we report a comprehensive analysis to discover different patterns of subclonal behaviors in functional modalities and signaling pathways out of heterogeneous population derived from a patient with lung squamous cell carcinoma, using single-cell mRNA sequencing. As a result of nonnegative matrix factorization as a clustering, we identified discrete 4 subgroups with a major group in accordance with overall expression profile of a pooled population of cells, and the other 3 minor groups that were masked in a pooled sample. Genomic variants were also reliably identified and compared across single cells. We integrated these genomic signatures from single cells to address the different responses in drug screening. Together, our approach provides insights into the more accurate strategy to identify minor but potentially important subclones that are relevant to drug resistance. Citation Format: Kyu-Tae Kim, Hye-Won Lee, Kyeung Min Joo, Sang-Chul Kim, Jin-Ku Lee, Nakho Chang, Jason K. Sa, Yu Jin Cho, Do-Hyun Nam, Hae-Ock Lee, Woong-Yang Park. Single-cell transcriptome analysis on lung squamous cell carcinoma derived from a patient. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4664. doi:10.1158/1538-7445.AM2014-4664

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