Investigation of IGF2, Hedgehog and fusion gene expression profiles in pediatric sarcomas.
The childhood sarcomas are malignant tumors with high mortality rates. They are divided into two genetic categories: a category without distinct pattern karyotypic changes and the other category showing unique translocations that originate gene rearrangements. This category includes rhabdomyosarcoma (RMS), Ewing's sarcoma (ES) and synovial sarcoma (SS). Diverse studies have related development genes, such as; IGF2, IHH, PTCH1 and GLI1 and sarcomatogenesis.


OBJECTIVE
To characterize the RMS, ES and SS rearrangements, we quantify the expression of IGF2 IHH, PTCH1 and GLI1 genes and correlate molecular data with clinical parameters of patients.


METHODS
We analyzed 29 RMS, 10 SS and 60 ES tumor samples by RT-PCR (polymerase chain reaction-reverse transcription) and qPCR (quantitative PCR).


RESULTS
Among the samples of ARMS, 50% had rearrangements of PAX3/7-FOXO1, 60% of ES samples were EWS-FLI1 positive and 90% of SS samples were positive for SS18-SSX1/2. In relation to the control reference samples (QPCR Human Reference Total RNA-Stratagene, Human Skeletal Muscle Total RNA-Ambion, Universal RNA Human Normal Tissues-Ambion), RMS samples showed a high IGF2 gene expression (p<0.0001). Moreover, ES samples showed a low IGF2 gene expression (p<0.0001) and high IHH (p<0.0001), PTCH1 (p=0.0173) and GLI1 (p=0.0113) gene expressions.


CONCLUSIONS
The molecular characterization of IGF and Hedgehog pathway in these pediatric sarcomas may collaborate to enable a better understanding of the biological behavior of these neoplasms.
Pediatric Oncology Institute (GRAACC), Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil; Department of Structural and Functional Biology, Federal University of São Paulo, São Paulo, SP, Brazil. Electronic address: rramos.souza@hotmail.com.
Robson Ramos
RR
de Souza
Pediatric Oncology Institute (GRAACC), Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil; Department of Structural and Functional Biology, Federal University of São Paulo, São Paulo, SP, Brazil. Electronic address: indhiradias@graacc.org.br.
Indhira Dias
ID
Oliveira
Pediatric Oncology Institute (GRAACC), Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil. Electronic address: mariopaniago@graacc.org.br.
Mario
M
del Giúdice Paniago
Pediatric Oncology Institute (GRAACC), Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil; Department of Structural and Functional Biology, Federal University of São Paulo, São Paulo, SP, Brazil. Electronic address: fernando.yaoita@gmail.com.
Fernando Hideki Kato
FH
Yaoita
Pediatric Oncology Institute (GRAACC), Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil. Electronic address: elianacaran@graacc.org.br.
Eliana Maria Monteiro
EM
Caran
Pediatric Oncology Institute (GRAACC), Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil. Electronic address: carladonatomacedo@uol.com.br.
Carla Renata Pacheco Donato
CR
Macedo
Pediatric Oncology Institute (GRAACC), Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil. Electronic address: sergiopetrilli@graacc.org.br.
Antonio Sergio
AS
Petrilli
Pediatric Oncology Institute (GRAACC), Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil; Division of Pediatric Surgery, Federal University of São Paulo, São Paulo, SP, Brazil. Electronic address: simoneabib@uol.com.br.
Simone de Campos Vieira
Sde C
Abib
Pediatric Oncology Institute (GRAACC), Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil; Department of Pathology, Federal University of São Paulo, São Paulo, SP, Brazil. Electronic address: mtseixas@patologia.epm.br.
Maria Teresa
MT
de Seixas Alves
Pediatric Oncology Institute (GRAACC), Department of Pediatrics, Federal University of São Paulo, São Paulo, SP, Brazil; Department of Structural and Functional Biology, Federal University of São Paulo, São Paulo, SP, Brazil. Electronic address: silviatoledo@graacc.org.br.
Silvia Regina Caminada
SR
de Toledo
D000293:Adolescent; D000328:Adult; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000235:genetics; D012509:Sarcoma / Q000235:genetics*; D012512:Sarcoma, Ewing / Q000235:genetics; D013584:Sarcoma, Synovial / Q000235:genetics; D059467:Transcriptome; D055815:Young Adult
D053823:Hedgehog Proteins; D015514:Oncogene Proteins, Fusion; D007335:Insulin-Like Growth Factor II
Ewing sarcoma; Gene expression; Gene fusions; IGF2 gene; Pediatric sarcomas; Rhabdomyosarcoma; Soft tissue tumors; Synovial sarcoma