Microenvironmental changes co-occur with mosaic somatic clonal expansions in normal skin and esophagus tissues

C Munugula; J Hu; E Christodoulou; V Yellapantula

doi:10.3389/fonc.2022.1021940

Microenvironmental changes co-occur with mosaic somatic clonal expansions in normal skin and esophagus tissues

Front Oncol. 2022 Dec 1:12:1021940. doi: 10.3389/fonc.2022.1021940. eCollection 2022.

Authors

C Munugula¹, J Hu¹, E Christodoulou¹, V Yellapantula^{1

2}

Affiliations

¹ Center for Personalized Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States.
² Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.

Abstract

The presence of somatic mutations, previously identified in cancers, are being increasingly recognized in normal tissues. While the role of microenvironment (ME) in tumor progression is well understood, the changes that occur in the microenvironment of normal tissues that harbor somatic mutations has not been systematically studied. Here, using normal RNA-Seq data accrued from 6544 samples across 27 tissue types from Genotype-Tissue Expression (GTEx) project, we studied the association of microenvironmental changes in the presence of somatic clonal expansions of previously implicated cancer genes. We focused our analysis on skin and esophagus since they have the highest number of samples and mutation burden together. We observed changes in microenvironmental cell-types previously implicated in tumor progression including endothelial cells, epithelial cells, pericytes, fibroblasts, chondrocytes, among others. The Epithelial-Mesenchymal-Transition (EMT) pathway is dysregulated in both skin and esophagus, along with increased hypoxia scores in samples with clonal expansions. These results suggest that microenvironmental changes play an important role in clonal expansions and potentially the initiating stages of cancer progression. Studying these changes may provide new avenues for early intervention of cancer, for targeted therapies, or enhance activities of conventional therapies.

Keywords: ageing and cancer; bioinforamtics; computation biology; genomics; microenvironment.