ArticleInternational journal of clinical oncology2020
TERT promotor region rearrangements analyzed in high-risk neuroblastomas by FISH method and whole genome sequencing.
Article in International journal of clinical oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundUnfavorable neuroblastomas (NBLs) achieve telomere stabilization via telomerase activation through MYCN amplification, TERT promoter region (TERT-PR) rearrangements, or alternative telomere lengthening of telomeres. No well-established methods are available for investigating TERT-PR rearrangements. We examined the relationship between and prognosis by fluorescence in situ hybridization (FISH) upstream and downstream of TERT to establish a simple analysis method. PROCEDURE: TERT-PR rearrangements were analyzed in 3 M MYCN amplified cases and, 11MYCN non-amplified cases (1 MS case, 1 L2 case and 2 M cases less than 18 months, and 1 L2 case and 6 M cases over 18 months old at diagnosis) to determine if MYCN and TERT-PR rearrangement were independent prognostic factors. In total, 14 patients (11 males, 3 females; median age 36.4 months, range 1-122 months) with NBLs were evaluated at Hiroshima University. We identified MYCN amplification, TERT expression, and TERT-PR rearrangements. TERT-PR rearrangement was detected by FISH upstream and downstream of TERT on Chr5.p15.33. For TERT-PR rearranged cases, we characterized the fusion partners by whole genome sequencing.
resultsWe detected TERT-PR rearrangements in two NBL samples. Both samples were high-risk NBLs and MYCN single NBLs, and their TERT expression levels were extremely higher than in the other samples. Genomic translocation occurred at chromosome 5p15.33 according to whole genome sequencing, agreeing with the FISH results. One case showed translocation of the chr5.p15.33 SLCA6A19 gene to 22q12.3, and another case showed chr5p15.33 to chr5q33.3.
conclusionsFISH is a useful diagnostic tool for evaluating high-risk NBLs in which TERT-PR rearrangements have occurred.
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