PMID- 32894394
OWN - NLM
STAT- MEDLINE
DCOM- 20210114
LR  - 20220302
IS  - 1437-7772 (Electronic)
IS  - 1341-9625 (Linking)
VI  - 25
IP  - 12
DP  - 2020 Dec
TI  - TERT promotor region rearrangements analyzed in high-risk neuroblastomas by FISH 
      method and whole genome sequencing.
PG  - 2166-2174
LID - 10.1007/s10147-020-01773-z [doi]
AB  - 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.
FAU - Kawashima, Masumi
AU  - Kawashima M
AD  - Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, Japan.
AD  - Graduate School of Biomedical and Health Sciences, Hiroshima University, 
      Hiroshima, Japan.
FAU - Ueda, Yuka
AU  - Ueda Y
AD  - Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, Japan.
AD  - Graduate School of Biomedical and Health Sciences, Hiroshima University, 
      Hiroshima, Japan.
FAU - Kurihara, Sho
AU  - Kurihara S
AD  - Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, Japan.
AD  - Graduate School of Biomedical and Health Sciences, Hiroshima University, 
      Hiroshima, Japan.
FAU - Hiyama, Eiso
AU  - Hiyama E
AUID- ORCID: 0000-0001-9179-5037
AD  - Department of Pediatric Surgery, Hiroshima University Hospital, Hiroshima, Japan. 
      eiso@hiroshima-u.ac.jp.
AD  - Graduate School of Biomedical and Health Sciences, Hiroshima University, 
      Hiroshima, Japan. eiso@hiroshima-u.ac.jp.
AD  - Natural Science Center for Basic Research and Development (N-BARD), Hiroshima 
      University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. 
      eiso@hiroshima-u.ac.jp.
LA  - eng
GR  - Scientific Research (A) (No. 15H02567)/Ministry of Education, Culture, Sports, 
      and Science of Japan/
GR  - 19ck0106332h0003/Japan Agency for Medical Research and Development/
PT  - Journal Article
DEP - 20200907
PL  - Japan
TA  - Int J Clin Oncol
JT  - International journal of clinical oncology
JID - 9616295
RN  - EC 2.7.7.49 (TERT protein, human)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Gene Rearrangement
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Infant
MH  - Male
MH  - Neuroblastoma/*genetics
MH  - Prognosis
MH  - Promoter Regions, Genetic
MH  - Telomerase/*genetics
MH  - Tumor Cells, Cultured
MH  - Whole Genome Sequencing/*methods
OTO - NOTNLM
OT  - Fluorescence in situ hybridization
OT  - Neuroblastoma
OT  - Rearrangement
OT  - TERT
EDAT- 2020/09/08 06:00
MHDA- 2021/01/15 06:00
CRDT- 2020/09/07 12:12
PHST- 2020/05/10 00:00 [received]
PHST- 2020/08/10 00:00 [accepted]
PHST- 2020/09/08 06:00 [pubmed]
PHST- 2021/01/15 06:00 [medline]
PHST- 2020/09/07 12:12 [entrez]
AID - 10.1007/s10147-020-01773-z [pii]
AID - 10.1007/s10147-020-01773-z [doi]
PST - ppublish
SO  - Int J Clin Oncol. 2020 Dec;25(12):2166-2174. doi: 10.1007/s10147-020-01773-z. 
      Epub 2020 Sep 7.