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Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
MAPK7 variants related to prognosis and chemotherapy response in osteosarcoma
Francine Tesser-Gamba1, Alini Trujillo Paolillo2, Mario Del Giúdice Paniago3
1Pediatric Oncology Institute (GRAACC), Federal University of São Paulo, Department of Pediatrics, São Paulo, SP, Brazil; Federal University of São Paulo, Department of Morphology and Genetics, São Paulo, SP, Brazil.
Abstract:
Osteosarcoma (OS) is a class of cancer originating from the bone, affecting mainly children and young adults. Our previous study showed that MAPK7 gene overexpression was significantly associated with tumor progression, poor treatment response, and worse overall survival, suggesting that MAPK7 could play an important role in OS tumorigenesis. We have investigated if MAPK7 overexpression was a result of any genomic changes in OS tumor specimens. We identified five SNPs (Single Nucleotide Polymorphism) previously described in databases, dbSNP and COSMIC, and identified two single nucleotide substitution not yet described. We found, in prechemotherapy specimens, a significant association of MAPK7 rs2233072G allele variant with metastasis at diagnosis and relapse (0.0909 and 0.0455, respectively). In post-chemotherapy, rs1054206GG specimen's genotype was associated with osteoblastic histological type (P= 0.0249) and presented decreased MAPK7 gene expression when compared with pre-chemotherapy specimens of same patients (P = 0.0095). Interestingly, it was observed some SNPs genotype exchange after chemotherapy. Our data indicated that MAPK7 gene expression associated with genotype exchange after chemotherapy, and these SNPs associated with important clinical parameters might be a valuable indicator for predicting in OS.
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