Genomics-guided drawing of malignant regulatory signatures revealed a pivotal role of human stem cell-associated retroviral sequences (SCARS) and functionally-active hESC enhancers

TL;DR

This paper explores the role of human stem cell-associated retroviral sequences (SCARS) and active enhancers in the origin, diagnosis, and potential treatment of lethal cancers, emphasizing their regulatory and diagnostic significance.

Contribution

It introduces the pivotal role of SCARS and active enhancers in malignant regulation, proposing their use as diagnostic markers and therapeutic targets.

Findings

SCARS are crucial in maintaining stemness during embryogenesis.

De-repression of SCARS leads to differentiation defects and malignancies.

Active SCARS signals can serve as diagnostic and therapeutic targets.

Abstract

From patients and physicians perspectives, the clinical definition of a tumor malignant phenotype could be restricted to the early diagnosis of sub-types of malignancies with the increased risk of existing therapy failure and high likelihood of death from cancer. It is the viewpoint from which the understanding of malignant regulatory signatures is considered in this contribution. Analyses from this perspective of experimental and clinical observations revealed the pivotal role of human stem cell-associated retroviral sequences (SCARS) in the origin and pathophysiology of clinically-lethal malignancies. SCARS represent evolutionary- and biologically-related family of genomic regulatory sequences, the principal physiological function of which is to create and maintain the stemness phenotype during human preimplantation embryogenesis. SCARS expression must be silenced during cellular differentiation and SCARS activity remains silent in most terminally-differentiated human cells performing specialized functions in the human body. De-repression and sustained activation of SCARS result in differentiation-defective phenotypes, tissue- and organ-specific clinical manifestations of which are diagnosed as pathological conditions defined by a consensus of pathomorphological, molecular, and genetic examinations as the malignant growth. Contemporary evidence are presented that high-fidelity molecular signals of continuing activities of SCARS in association with genomic regulatory networks of thousands functionally-active enhancers triggering engagements of down-stream genetic loci may serve as both reliable diagnostic tools and druggable molecular targets readily amenable for diagnosis and efficient therapeutic management of clinically-lethal malignancies.