Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas
Abstract Pediatric solid tumors are a heterogeneous group of neoplasms with over 100 subtypes. Clinical and histopathological diagnosis remains challenging due to the overlapping morphological and immunohistochemical findings and the presence of atypical cases. To evaluate the potential utility of i...
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Nature Portfolio
2021
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oai:doaj.org-article:29a8e03506ee4c179df83a3260a0ed052021-12-02T17:41:29ZIntegrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas10.1038/s41525-021-00210-y2056-7944https://doaj.org/article/29a8e03506ee4c179df83a3260a0ed052021-06-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00210-yhttps://doaj.org/toc/2056-7944Abstract Pediatric solid tumors are a heterogeneous group of neoplasms with over 100 subtypes. Clinical and histopathological diagnosis remains challenging due to the overlapping morphological and immunohistochemical findings and the presence of atypical cases. To evaluate the potential utility of including RNA-sequencing (RNA-seq) in the diagnostic process, we performed RNA-seq in 47 patients with suspected pediatric sarcomas. Histopathologists specialized in pediatric cancer re-evaluated pathological specimens to reach a consensus diagnosis; 42 patients were diagnosed with known subtypes of solid tumors whereas 5 patients were diagnosed with undifferentiated sarcoma. RNA-seq analysis confirmed and refined consensus diagnoses and further identified diagnostic genetic variants in four of the five patients with undifferentiated sarcoma. Genetic lesions were detected in 23 patients, including the novel SMARCA4-THOP1 fusion gene and 22 conventional or recently reported genetic events. Unsupervised clustering analysis of the RNA-seq data identified a distinct cluster defined by the overexpression of rhabdomyosarcoma-associated genes including MYOG and CHRNG. These findings suggest that RNA-seq-based genetic analysis may aid in the diagnosis of suspected pediatric sarcomas, which would be useful for the development of stratified treatment strategies.Daisuke IchikawaKyoko YamashitaYusuke OkunoHideki MuramatsuNorihiro MurakamiKyogo SuzukiDaiei KojimaShinsuke KataokaMotoharu HamadaRieko TaniguchiEri NishikawaNozomu KawashimaAtsushi NaritaNobuhiro NishioAsahito HamaKenji KasaiSeiji MizunoYoshie ShimoyamaMasato NakaguroHajime OkitaSeiji KojimaAtsuko NakazawaYoshiyuki TakahashiNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-10 (2021) |
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DOAJ |
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Medicine R Genetics QH426-470 |
| spellingShingle |
Medicine R Genetics QH426-470 Daisuke Ichikawa Kyoko Yamashita Yusuke Okuno Hideki Muramatsu Norihiro Murakami Kyogo Suzuki Daiei Kojima Shinsuke Kataoka Motoharu Hamada Rieko Taniguchi Eri Nishikawa Nozomu Kawashima Atsushi Narita Nobuhiro Nishio Asahito Hama Kenji Kasai Seiji Mizuno Yoshie Shimoyama Masato Nakaguro Hajime Okita Seiji Kojima Atsuko Nakazawa Yoshiyuki Takahashi Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas |
| description |
Abstract Pediatric solid tumors are a heterogeneous group of neoplasms with over 100 subtypes. Clinical and histopathological diagnosis remains challenging due to the overlapping morphological and immunohistochemical findings and the presence of atypical cases. To evaluate the potential utility of including RNA-sequencing (RNA-seq) in the diagnostic process, we performed RNA-seq in 47 patients with suspected pediatric sarcomas. Histopathologists specialized in pediatric cancer re-evaluated pathological specimens to reach a consensus diagnosis; 42 patients were diagnosed with known subtypes of solid tumors whereas 5 patients were diagnosed with undifferentiated sarcoma. RNA-seq analysis confirmed and refined consensus diagnoses and further identified diagnostic genetic variants in four of the five patients with undifferentiated sarcoma. Genetic lesions were detected in 23 patients, including the novel SMARCA4-THOP1 fusion gene and 22 conventional or recently reported genetic events. Unsupervised clustering analysis of the RNA-seq data identified a distinct cluster defined by the overexpression of rhabdomyosarcoma-associated genes including MYOG and CHRNG. These findings suggest that RNA-seq-based genetic analysis may aid in the diagnosis of suspected pediatric sarcomas, which would be useful for the development of stratified treatment strategies. |
| format |
article |
| author |
Daisuke Ichikawa Kyoko Yamashita Yusuke Okuno Hideki Muramatsu Norihiro Murakami Kyogo Suzuki Daiei Kojima Shinsuke Kataoka Motoharu Hamada Rieko Taniguchi Eri Nishikawa Nozomu Kawashima Atsushi Narita Nobuhiro Nishio Asahito Hama Kenji Kasai Seiji Mizuno Yoshie Shimoyama Masato Nakaguro Hajime Okita Seiji Kojima Atsuko Nakazawa Yoshiyuki Takahashi |
| author_facet |
Daisuke Ichikawa Kyoko Yamashita Yusuke Okuno Hideki Muramatsu Norihiro Murakami Kyogo Suzuki Daiei Kojima Shinsuke Kataoka Motoharu Hamada Rieko Taniguchi Eri Nishikawa Nozomu Kawashima Atsushi Narita Nobuhiro Nishio Asahito Hama Kenji Kasai Seiji Mizuno Yoshie Shimoyama Masato Nakaguro Hajime Okita Seiji Kojima Atsuko Nakazawa Yoshiyuki Takahashi |
| author_sort |
Daisuke Ichikawa |
| title |
Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas |
| title_short |
Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas |
| title_full |
Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas |
| title_fullStr |
Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas |
| title_full_unstemmed |
Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas |
| title_sort |
integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/29a8e03506ee4c179df83a3260a0ed05 |
| work_keys_str_mv |
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1718379634484051968 |