Description

Histopathology Linked Single-cell Genomics by High-throughput Laser Discharging System

Sungsik Kim¹, Amos C. Lee¹, Sangwwok Bae¹, Veronica Kim², Hyojung Park², Ji Yeoun Lee^2,3, Sunghoon Kwon¹

¹Interdisciplinary Program for Bioengineering, Seoul National University College of Engineering; ²Department of Anatomy, Seoul National University College of Medicine;

³Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital

Modern oncology lies its foundations on histopathology. However, limited number of molecular targets often fail to identify sub-clones or rare-clones of caner and subjective nature of pathological inspection may produce misunderstandings of cancer. Recent advances in sequencing technology have revolutionized oncology, providing opportunity to overcome the limitations that pathology have. Here, we describe Phenotype based High-throughput Laser Isolation and Sequencing (PHLI-seq), which can efficiently find cancer subclonality and rare variants with high sensitivity and accuracy, preserving information of spatial organization and phenotype of cells.

We developed Phenotype based High-throughput Laser Isolation and Sequencing (PHLI-seq) for mapping genomics to tissue context. We applied this method to explore genetic heterogeneity of a HER2 positive breast cancer tissue. We performed whole genome sequencing(WGS) to detect copy number variation(CNV), and whole exome sequencing (WES) and Targeted sequencing to find somatic variants. Overall, we resolved three subclones and their genetic alterations in the HER2 positive breast cancer, and their spatial organization.