TY - JOUR
T1 - The search for molecular markers in a gene-orphan case study of a pediatric spinal cord pilocytic astrocytoma
AU - Martinelli, Carolina
AU - Gabriele, Fabio
AU - Manai, Federico
AU - Ciccone, Roberto
AU - Novara, Francesca
AU - Sauta, Elisabetta
AU - Bellazzi, Riccardo
AU - Patane, Monica
AU - Moroni, Isabella
AU - Paterra, Rosina
AU - Comincini, Sergio
N1 - Funding Information:
This research was supported by the Italian Ministry of Education, University and Research (MIUR): Dipartimenti di Eccellenza Program (2018-2022) - Dept. of Biology and Biotechnology “L. Spallanzani”, University of Pavia (to SC). RC was supported by a Grant of the Italian Ministry of Education, University and Research (MIUR) to the Department of Molecular Medicine of the University of Pavia under the initiative “Dipartimenti di Eccellenza (2018-2022)”.
Publisher Copyright:
© 2020 International Institute of Anticancer Research. All rights reserved.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Background/Aim: We herein presented a case of pediatric spinal cord pilocytic astrocytoma diagnosed on the basis of histopathological and clinical findings. Materials and Methods: Given the paucity of data on genetic features for this tumor, we performed exome, array CGH and RNA sequencing analysis from nucleic acids isolated from a unique and not repeatable very small amount of a formalin-fixed, paraffin-embedded (FFPE) specimen. Results: DNA mutation analysis, comparing tumor and normal lymphocyte peripheral DNA, evidenced few tumor-specific single nucleotide variants in DEFB119, MUC5B, NUDT1, LTBP3 and CPSF3L genes. Differently, tumor DNA was not characterized by for the main pilocytic astrocytoma gene variations, including BRAFV600E. An inframe trinucleotides insertion involving DLX6 or lnc DLX6-AS1 genes was scored in 44.9% of sequenced reads; the temporal profile of this variation on the expression of DLX-AS1 was investigated in patient`s urine-derived exosomes, reporting no significant variation in the one-year molecular follow-up. Array CGH identified a tumor microdeletion at the 6q25.3 chromosomal region, spanning 1,01 Mb and comprising ZDHHC14, SNX9, TULP4 and SYTL3 genes. The expression of these genes did not change in urine-derived exosomes during the one-year investigation period. Finally, RNAseq did not reveal any of the common pilocytic BRAF-KIAA1549 genes fusion events. Conclusion: To our knowledge, the present report is one of the first described gene-orphan case studies of a pediatric spinal cord pilocytic astrocytoma.
AB - Background/Aim: We herein presented a case of pediatric spinal cord pilocytic astrocytoma diagnosed on the basis of histopathological and clinical findings. Materials and Methods: Given the paucity of data on genetic features for this tumor, we performed exome, array CGH and RNA sequencing analysis from nucleic acids isolated from a unique and not repeatable very small amount of a formalin-fixed, paraffin-embedded (FFPE) specimen. Results: DNA mutation analysis, comparing tumor and normal lymphocyte peripheral DNA, evidenced few tumor-specific single nucleotide variants in DEFB119, MUC5B, NUDT1, LTBP3 and CPSF3L genes. Differently, tumor DNA was not characterized by for the main pilocytic astrocytoma gene variations, including BRAFV600E. An inframe trinucleotides insertion involving DLX6 or lnc DLX6-AS1 genes was scored in 44.9% of sequenced reads; the temporal profile of this variation on the expression of DLX-AS1 was investigated in patient`s urine-derived exosomes, reporting no significant variation in the one-year molecular follow-up. Array CGH identified a tumor microdeletion at the 6q25.3 chromosomal region, spanning 1,01 Mb and comprising ZDHHC14, SNX9, TULP4 and SYTL3 genes. The expression of these genes did not change in urine-derived exosomes during the one-year investigation period. Finally, RNAseq did not reveal any of the common pilocytic BRAF-KIAA1549 genes fusion events. Conclusion: To our knowledge, the present report is one of the first described gene-orphan case studies of a pediatric spinal cord pilocytic astrocytoma.
KW - Bioinformatics
KW - Chromosomal abnormalities
KW - DNA mutations
KW - Exome analysis
KW - Pediatric astrocytic tumors
UR - http://www.scopus.com/inward/record.url?scp=85081574462&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081574462&partnerID=8YFLogxK
U2 - 10.21873/cgp.20172
DO - 10.21873/cgp.20172
M3 - Article
C2 - 32108034
AN - SCOPUS:85081574462
VL - 17
SP - 117
EP - 130
JO - Cancer Genomics and Proteomics
JF - Cancer Genomics and Proteomics
SN - 1109-6535
IS - 2
ER -