Pediatric 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.
Pediatric Oncology Institute (GRAACC), Federal University of São Paulo, Department of Pediatrics, São Paulo, SP, Brazil; Federal University of São Paulo, Department of Clinical and Experimental Oncology, São Paulo, SP, Brazil.
Ann Diagn Pathol. 2020 Jun;46:151482. doi: 10.1016/j.anndiagpath.2020.151482. Epub 2020 Feb 19.
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.
骨肉瘤(OS)是一种起源于骨骼的癌症,主要影响儿童和青少年。我们之前的研究表明,MAPK7 基因的过表达与肿瘤进展、治疗反应差和总体生存率差显著相关,这表明 MAPK7 可能在 OS 肿瘤发生中发挥重要作用。我们已经研究了 MAPK7 的过表达是否是 OS 肿瘤标本中任何基因组变化的结果。我们在数据库 dbSNP 和 COSMIC 中鉴定了五个先前描述的单核苷酸多态性(SNP),并鉴定了两个尚未描述的单核苷酸替换。我们发现,在化疗前标本中,MAPK7 rs2233072G 等位基因变异与诊断时转移和复发显著相关(分别为 0.0909 和 0.0455)。在化疗后,rs1054206GG 标本的基因型与成骨组织学类型相关(P=0.0249),并且与同一患者化疗前标本相比,MAPK7 基因表达降低(P=0.0095)。有趣的是,在化疗后观察到一些 SNP 基因型交换。我们的数据表明,MAPK7 基因表达与化疗后基因型交换有关,这些与重要临床参数相关的 SNPs 可能是预测 OS 的有价值指标。