Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Identification of Key Proteins in the Alternative Lengthening of Telomeres Associated Promyelocytic Leukemia Nuclear Bodies

Version 1 : Received: 30 September 2021 / Approved: 1 October 2021 / Online: 1 October 2021 (08:18:18 CEST)

A peer-reviewed article of this Preprint also exists.

Armendáriz-Castillo, I.; Hidalgo-Fernández, K.; Pérez-Villa, A.; García-Cárdenas, J.M.; López-Cortés, A.; Guerrero, S. Identification of Key Proteins from the Alternative Lengthening of Telomeres-Associated Promyelocytic Leukemia Nuclear Bodies Pathway. Biology 2022, 11, 185. https://doi.org/10.3390/biology11020185 Armendáriz-Castillo, I.; Hidalgo-Fernández, K.; Pérez-Villa, A.; García-Cárdenas, J.M.; López-Cortés, A.; Guerrero, S. Identification of Key Proteins from the Alternative Lengthening of Telomeres-Associated Promyelocytic Leukemia Nuclear Bodies Pathway. Biology 2022, 11, 185. https://doi.org/10.3390/biology11020185

Journal reference: Biology 2022, 11, 1-17
DOI: 10.3390/biology11020185

Abstract

One of the hallmarks of the Alternative Lengthening of Telomeres (ALT) is the association with Promyelocytic Leukemia (PML) Nuclear Bodies, known as APBs. In the last years, APBs have been described as the main place where telomeric extension occurs in ALT positive cancer cell lines. A different set of proteins have been associated with APBs function, however, the molecular mechanisms behind their assembly, colocalization, and clustering of telomeres, among others, remain unclear. To improve the understanding of APBs in the ALT pathway, we integrated multi-omics analyses to evaluate genomic, transcriptomic and proteomic alterations, and functional interactions of 71 APBs-related genes/proteins in 32 PanCancer Atlas studies from The Cancer Genome Atlas Consortium (TCGA). As a result, we identified 13 key proteins which showed distinctive mutations, interactions, and functional enrichment patterns across all the cancer types and proposed this set of proteins as candidates for future ex vivo and in vivo analyses that will validate these proteins to improve the understanding of the ALT pathway, fill the current research gap about APBs function and their role in ALT, and be considered as potential therapeutic targets for the diagnosis and treatment of ALT positive cancers in the future.

Keywords

ALT; PML; Telomeres; Pan-Cancer; TCGA

Subject

LIFE SCIENCES, Molecular Biology

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