TY - JOUR
T1 - Integrated diagnosis based on transcriptome analysis in suspected pediatric sarcomas
AU - Ichikawa, Daisuke
AU - Yamashita, Kyoko
AU - Okuno, Yusuke
AU - Muramatsu, Hideki
AU - Murakami, Norihiro
AU - Suzuki, Kyogo
AU - Kojima, Daiei
AU - Kataoka, Shinsuke
AU - Hamada, Motoharu
AU - Taniguchi, Rieko
AU - Nishikawa, Eri
AU - Kawashima, Nozomu
AU - Narita, Atsushi
AU - Nishio, Nobuhiro
AU - Hama, Asahito
AU - Kasai, Kenji
AU - Mizuno, Seiji
AU - Shimoyama, Yoshie
AU - Nakaguro, Masato
AU - Okita, Hajime
AU - Kojima, Seiji
AU - Nakazawa, Atsuko
AU - Takahashi, Yoshiyuki
N1 - Funding Information:
The authors would like to thank all of the clinicians, patients, and their families. The authors would also like to thank Ms. Yoshie Miura, Ms. Hiroko Ono, Ms. Yuko Imanishi, and Ms. Hiroe Namizaki for their valuable assistance. The authors acknowledge the Division for Medical Research Engineering, Nagoya University Graduate School of Medicine for technical support and the Human Genome Center, Institute of Medical Science, the University of Tokyo (http://sc.hgc.jp/shirokane.html) for providing supercomputing resources. This work was supported in part by a grant from the National Center for Child Health and Development of Japan (26-20).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41525-021-00210-y
DO - 10.1038/s41525-021-00210-y
M3 - Article
AN - SCOPUS:85108099571
VL - 6
JO - npj Genomic Medicine
JF - npj Genomic Medicine
SN - 2056-7944
IS - 1
M1 - 49
ER -