TERT promotor region rearrangements analyzed in high-risk neuroblastomas by FISH method and whole genome sequencing.
Int J Clin Oncol
; 25(12): 2166-2174, 2020 Dec.
Article
en En
| MEDLINE
| ID: mdl-32894394
ABSTRACT
BACKGROUND:
Unfavorable 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.RESULTS:
We 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.CONCLUSIONS:
FISH is a useful diagnostic tool for evaluating high-risk NBLs in which TERT-PR rearrangements have occurred.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hibridación Fluorescente in Situ
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Telomerasa
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Secuenciación Completa del Genoma
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Neuroblastoma
Tipo de estudio:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Int J Clin Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón