{"title":"荧光原位杂交鉴定具有TERT重排的神经母细胞瘤的转化实践。","authors":"Yongbo Yu, Meng Zhang, Xingfeng Yao, Xiaoxing Guan, Chao Jia, Ping Chu, Ruqian Zhang, Yeran Yang, Yaqiong Jin, Huanmin Wang, Xin Ni, Lejian He, Yongli Guo","doi":"10.1002/cjp2.338","DOIUrl":null,"url":null,"abstract":"<p>Recently, <i>telomerase reverse transcriptase</i> (<i>TERT</i>) gene rearrangements have been identified in neuroblastoma (NB), the typical pathological type of neuroblastic tumours (NTs); however, the prevalence of <i>TERT</i> rearrangements in other types of NT remains unknown. This study aimed to develop a practical method for detecting <i>TERT</i> defects and to evaluate the clinical relevance of <i>TERT</i> rearrangements as a biomarker for NT prognosis. A <i>TERT</i> break-apart probe for fluorescence <i>in situ</i> hybridisation (FISH) was designed, optimised, and applied to assess the genomic status of <i>TERT</i> in Chinese children with NTs at the Beijing Children's Hospital from 2016 to 2019. Clinical, histological, and genetic characteristics of <i>TERT</i>-rearranged NTs were further addressed. Genomic <i>TERT</i> rearrangements could be effectively detected by FISH and were mutually exclusive with <i>MYCN</i> amplification. <i>TERT</i> rearrangements were identified in 6.0% (38/633) of NTs overall, but 12.4% (31/250) in high-risk patients. <i>TERT</i> rearrangements identified a subtype of aggressive NTs with the characteristics of Stage 3/4, high-risk category, over 18 months old, and presenting all histological subtypes of NB and ganglioneuroblastoma nodular. Moreover, <i>TERT</i> rearrangements were significantly associated with elevated <i>TERT</i> expression levels and decreased survival chances. Multivariable analysis confirmed that it was an independent prognostic marker for NTs. FISH is an easily applicable method for evaluating <i>TERT</i> defects, which define a subgroup of NTs with unfavourable prognosis. <i>TERT</i> rearrangements would contribute to characterising NT molecular signatures in clinical practice.</p>","PeriodicalId":48612,"journal":{"name":"Journal of Pathology Clinical Research","volume":"9 6","pages":"475-487"},"PeriodicalIF":3.4000,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/e3/CJP2-9-475.PMC10556277.pdf","citationCount":"0","resultStr":"{\"title\":\"Translational practice of fluorescence in situ hybridisation to identify neuroblastic tumours with TERT rearrangements\",\"authors\":\"Yongbo Yu, Meng Zhang, Xingfeng Yao, Xiaoxing Guan, Chao Jia, Ping Chu, Ruqian Zhang, Yeran Yang, Yaqiong Jin, Huanmin Wang, Xin Ni, Lejian He, Yongli Guo\",\"doi\":\"10.1002/cjp2.338\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Recently, <i>telomerase reverse transcriptase</i> (<i>TERT</i>) gene rearrangements have been identified in neuroblastoma (NB), the typical pathological type of neuroblastic tumours (NTs); however, the prevalence of <i>TERT</i> rearrangements in other types of NT remains unknown. This study aimed to develop a practical method for detecting <i>TERT</i> defects and to evaluate the clinical relevance of <i>TERT</i> rearrangements as a biomarker for NT prognosis. A <i>TERT</i> break-apart probe for fluorescence <i>in situ</i> hybridisation (FISH) was designed, optimised, and applied to assess the genomic status of <i>TERT</i> in Chinese children with NTs at the Beijing Children's Hospital from 2016 to 2019. Clinical, histological, and genetic characteristics of <i>TERT</i>-rearranged NTs were further addressed. Genomic <i>TERT</i> rearrangements could be effectively detected by FISH and were mutually exclusive with <i>MYCN</i> amplification. <i>TERT</i> rearrangements were identified in 6.0% (38/633) of NTs overall, but 12.4% (31/250) in high-risk patients. <i>TERT</i> rearrangements identified a subtype of aggressive NTs with the characteristics of Stage 3/4, high-risk category, over 18 months old, and presenting all histological subtypes of NB and ganglioneuroblastoma nodular. Moreover, <i>TERT</i> rearrangements were significantly associated with elevated <i>TERT</i> expression levels and decreased survival chances. Multivariable analysis confirmed that it was an independent prognostic marker for NTs. FISH is an easily applicable method for evaluating <i>TERT</i> defects, which define a subgroup of NTs with unfavourable prognosis. <i>TERT</i> rearrangements would contribute to characterising NT molecular signatures in clinical practice.</p>\",\"PeriodicalId\":48612,\"journal\":{\"name\":\"Journal of Pathology Clinical Research\",\"volume\":\"9 6\",\"pages\":\"475-487\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2023-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/e3/CJP2-9-475.PMC10556277.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Pathology Clinical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cjp2.338\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Pathology Clinical Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cjp2.338","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
Translational practice of fluorescence in situ hybridisation to identify neuroblastic tumours with TERT rearrangements
Recently, telomerase reverse transcriptase (TERT) gene rearrangements have been identified in neuroblastoma (NB), the typical pathological type of neuroblastic tumours (NTs); however, the prevalence of TERT rearrangements in other types of NT remains unknown. This study aimed to develop a practical method for detecting TERT defects and to evaluate the clinical relevance of TERT rearrangements as a biomarker for NT prognosis. A TERT break-apart probe for fluorescence in situ hybridisation (FISH) was designed, optimised, and applied to assess the genomic status of TERT in Chinese children with NTs at the Beijing Children's Hospital from 2016 to 2019. Clinical, histological, and genetic characteristics of TERT-rearranged NTs were further addressed. Genomic TERT rearrangements could be effectively detected by FISH and were mutually exclusive with MYCN amplification. TERT rearrangements were identified in 6.0% (38/633) of NTs overall, but 12.4% (31/250) in high-risk patients. TERT rearrangements identified a subtype of aggressive NTs with the characteristics of Stage 3/4, high-risk category, over 18 months old, and presenting all histological subtypes of NB and ganglioneuroblastoma nodular. Moreover, TERT rearrangements were significantly associated with elevated TERT expression levels and decreased survival chances. Multivariable analysis confirmed that it was an independent prognostic marker for NTs. FISH is an easily applicable method for evaluating TERT defects, which define a subgroup of NTs with unfavourable prognosis. TERT rearrangements would contribute to characterising NT molecular signatures in clinical practice.
期刊介绍：
The Journal of Pathology: Clinical Research and The Journal of Pathology serve as translational bridges between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies.
The focus of The Journal of Pathology: Clinical Research is the publication of studies that illuminate the clinical relevance of research in the broad area of the study of disease. Appropriately powered and validated studies with novel diagnostic, prognostic and predictive significance, and biomarker discover and validation, will be welcomed. Studies with a predominantly mechanistic basis will be more appropriate for the companion Journal of Pathology.
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