Abstract 121: In situ mutational mapping of tumor cells and tissues at subcellular resolution

• Published in: Cancer research (Chicago, Ill.) Ill.), 2023-04, Vol.83 (7_Supplement), p.121-121
• Main Authors: Östlin, Jessica, Chitnis, Debashish, Olofsson, Mimmi, Hernández-Neuta, Iván, Kuhnemund, Malte
• Format: Article
• Language: English
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2023-121

In situ techniques enable studying cells and tissues within their cellular context. This is of great importance in cancer, often displaying genetic and phenotypic heterogeneity with distinct subclones harboring different capacity to grow and spread. It was recently shown that by spatially mapping dozens of mutations within tumor tissues, tumor evolution and microenvironmental impact could be studied at the subclonal level (1). We have developed an in situ technique that spatially maps multiple expressed mutations simultaneously at subcellular resolution. The technique is based on single-nucleotide discriminating probes hybridized to mRNA. Correctly hybridized probes get ligated, amplified by rolling circle amplification, and decoded on our Xenium In situ platform. The technique was validated in well characterized cell lines, targeting multiple single nucleotide variants of the KRAS codons 12 and 13. As a proof of concept, we then applied the technique on FFPE breast tumor tissue sections that were previously characterized by targeted NGS onco-gene panels on extracted tumor DNA. In addition to the 280 plex Xenium Human Breast Gene Expression Panel, we targeted several mutations in situ and successfully mapped their spatial distribution in the tumor tissue sections. In summary, we demonstrate that the Xenium In Situ technology can spatially resolve the genetic and phenotypic landscape of breast tumors. The technology will enable researchers to unravel tumor evolution, growth and spread as well as the microenvironmental impact in detail, potentially refining patient stratification and treatment decisions. Citation Format: Jessica Östlin, Debashish Chitnis, Mimmi Olofsson, Iván Hernández-Neuta, Malte Kuhnemund. In situ mutational mapping of tumor cells and tissues at subcellular resolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 121.