TERT promotor region rearrangements analyzed in high-risk neuroblastomas by FISH method and whole genome sequencing
- PDF / 2,894,048 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 7 Downloads / 166 Views
ORIGINAL ARTICLE
TERT promotor region rearrangements analyzed in high‑risk neuroblastomas by FISH method and whole genome sequencing Masumi Kawashima1,2 · Yuka Ueda1,2 · Sho Kurihara1,2 · Eiso Hiyama1,2,3 Received: 10 May 2020 / Accepted: 10 August 2020 © Japan Society of Clinical Oncology 2020
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. Keywords TERT · Rearrangement · Neuroblastoma · Fluorescence in situ hybridization
Introduction Neuroblastoma (NBL) is one of famous pediatric malignant tumor. Some NBL cases are in good prognosis as natural regression course, on the other hand, other NBL cases are poor course as life-threatening. It is known that the malignant grade of NBL mainly depending on the biological * Eiso Hiyama eiso@hiroshima‑u.ac.jp 1
Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, Japan
2
Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
3
Natural Science Center for Basic Research and Development (N‑BARD), Hiroshima University, 1‑2‑3 Kasumi, Minami‑ku, Hiroshima 734‑8551, Japan
characteristics of the tumor cells [1]. MYCN amplification and chromosomal aberrations including 1p loss, 11q loss, and 17p gain have been reported as biological indicators as poor progressive factors [2, 3]. In NBL, telomere shortening is correlat
Data Loading...
