Abstract
BackgroundAlternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by a broad range of neoplasms to maintain telomere length, permitting uncontrolled replication during their progression. ALT has been described in different types of sarcoma, but a comprehensive analysis of its clinical significance is still lacking. Therefore, we provide here the first meta-analysis on this topic.MethodsWe searched SCOPUS and PubMed through July 2018 to identify all studies that investigated the prognostic role of ALT in sarcomas. We considered the risk of death (risk ratio, RR) calculated as the number of death vs. total participants during follow-up in ALT+ versus ALT- patients as the primary outcome. The secondary outcome was the hazard ratio (HR), adjusted for the maximum number of covariates available, using ALT- patients as reference.ResultsEight articles comprising a total of 551 patients with sarcomas (226 ALT+ and 325 ALT-) were selected. The ALT+ group showed a higher mitotic count and a higher tumor grade compared with the ALT- group (p < 0.01). Furthermore, we demonstrate a strong impact of ALT on survival. In fact, ALT+ patients showed a statistically significant higher risk of death than ALT- patients, when also considering data from multivariate analyses (RR = 1.50; 95% CI: 1.15–1.96; p = 0.003; HR = 2.02; 95% CI: 1.22–3.38; p = 0.007).ConclusionsOur results indicate that ALT is associated with an increased risk of death in patients with sarcoma. In these neoplasms, ALT should be taken into account for a precise prognostic stratification and design of potential therapeutic strategies.
Highlights
Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by a broad range of neoplasms to maintain telomere length, permitting uncontrolled replication during their progression
The ALT+ group comprised a higher proportion of women than ALT- (77% vs. 60%); ALT+ patients were older than ALT- (54.9 vs 50.9 years old), but these differences were not statistically significant
The present study demonstrates that ALT plays an important prognostic role in sarcoma, as it is associated with an increased risk of death
Summary
Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by a broad range of neoplasms to maintain telomere length, permitting uncontrolled replication during their progression. Each round of cell division is accompanied by telomere shortening [1, 2] This process is physiologically due to the inability of somatic cells to polymerize all DNA during replication. A recently proposed classification of these tumors distinguishes two classes of sarcomas, one with simple karyotypes involving specific genetic alterations, and one with complex and unbalanced karyotypes, usually involving non-specific genetic abnormalities, including copy number alterations [11] Despite such a complex molecular landscape, a relatively common cytogenetic anomaly of sarcomas, represented by ALT, has been demonstrated in both classes [12]. A comprehensive analysis of the clinical significance of ALT for this kind of neoplasms is still lacking To this end, we assessed the prognostic role of ALT in sarcomas by performing the first systematic review with meta-analysis on this topic
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