Dados do Resumo

Título

Exploring the relation between telomere size and CNAs in pediatric osteosarcomas and Ewing sarcomas

Introdução

Pediatric bone sarcomas comprise mesenchymal tumors with many genetics and epigenetics alterations as well as complex events that include copy number alterations (CNAs). It seems that there is a relation between a high number of structural events in the DNA and the telomere size. Telomeres consist of repetitive nucleotides sequences located at the end of chromosomes and are essential for maintaining chromosomal and genomic stability.

Objetivo

We aimed to explore the relationship between telomere size and the number of CNAs in pediatric bone sarcomas searching for an association with tumor progression.

Métodos

To quantify the relative length of telomeres, quantitative PCR (qPCR) using primers that amplify telomeric sequences and a reference sequence were tested in the samples. Data was analyzed using the Cawthon formula. Genes from telomere maintenance pathways were analyzed using whole exome sequencing data. Copy number alterations were extracted from methylation retrieved from the Epic BeadChip arrays (Illumina) using the Conumee package (Bioconductor) in R. Alterations types included balanced, focal, arm-level, chromosome-level, gain and loss. The data was analyzed using software using the package- Enhanced copy number variation analysis using Illumina DNA methylation arrays.

Resultados

Ewing sarcoma had an average of 23 chromosomal alterations (ranging from 22 to 27), mostly balanced and chromosome-level types. The t(11;22) is a driver alteration for Ewing sarcomas used to molecularly differentiate these from other tumor entities. Osteosarcoma presents a high number of copy number alterations, with an average of 41 alterations (22 to 63), suggesting that these tumors present genomic instability. There were no differences for Ewing sarcoma samples while osteosarcoma presented a wide size variation of the telomeres. Osteosarcoma with higher telomere size presented mutations in genes from the alternative telomere maintenance pathway.

Conclusões

Osteosarcoma has a higher number of copy number alterations compared to Ewing sarcoma, which may be related to the genomic instability usually described in this tumor type. Considering that telomeres are important for maintaining the genomic stability, it is plausible that an increase or decrease in the telomere size could contribute to the high number of DNA alterations that are usually found in these tumors. However, the relationship between telomere size and CNA in bone sarcomas still needs to be explored.

Financiador do resumo

FAPESP 2023/10527-8, FAPESP 2021/06782-7, CNPq 311141/2021-8

Palavras Chave

Telomere; copy number alteration; pediatric bone sarcomas