Genetic profiling of osteosarcoma in an adolescent using a next-generation sequencing panel and Sanger sequencing: A case report and review of the literature

被引:0
作者
Chantre-justino, Mariana [1 ]
Silvestre, Rafaele Tavares [2 ]
De Castro, Thiago Luz [2 ]
Luz, Eliane [3 ]
Pinheiro, Rafael De Castro E. Silva [3 ]
Caruso, Anabela [3 ]
Lopes, Ana Cristina De Sa [3 ]
Meohas, Walter [3 ]
Alves, Gilda [2 ]
Ornellas, Maria Helena Faria [2 ]
机构
[1] Natl Inst Traumatol & Orthoped, Res Div, 5th Floor 500 Ave Brazil, BR-20940070 Sao Cristovao, RJ, Brazil
[2] Univ Estado Rio De Janeiro, Fac Med Sci, Pathol Dept, Circulating Biomarkers Lab, BR-20550170 Rio De Janeiro, Brazil
[3] Natl Inst Traumatol & Orthoped, Specialized Care Ctr Orthoped Oncol, BR-20940070 Rio De Janeiro, Brazil
关键词
osteosarcoma; childhood cancer; next-generation sequencing; Sanger sequencing; TP53; MUTATIONS; CANCER; CHILDREN; THERAPY; PATIENT; MUTANT; P53;
D O I
10.3892/br.2025.1920
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Osteosarcoma (OS) is the most common malignant bone tumor affecting adolescents and young adults and it usually occurs in the long bones of the extremities. The detection of cancer-related genetic alterations has a growing effect in guiding diagnosis, prognosis and targeted therapies. However, little is known about the molecular aspects involved in the etiology and progression of OS, which limits options for targeted therapies. The present study described a case of an adolescent patient (16-years-old) who was diagnosed with conventional central OS in the right distal femur without the evidence of pulmonary metastases; the patient was treated with surgery and adjuvant chemotherapy. Genetic alterations in resected tumor tissue were investigated via next-generation sequencing (NGS) technology using a targeted NGS panel. Sanger sequencing was also performed to investigate somatic and germline TP53 mutations (exons 4-8). NGS analysis revealed an intratumor heterogeneity signature in OS tumor, including several single nucleotide variants identified in genes encoding tyrosine kinase proteins. No PCR products for TP53 exon 5 were detected in the tumor sample by PCR analysis prior to Sanger sequencing, suggesting a significant deletion in this exon. Sanger sequencing analysis revealed the missense variant TP53 c.712T>A (p.Cys238Ser) in tumor tissue sample, thus reinforcing the role of TP53 somatic mutations in OS development. Additionally, the TP53 c.215C>G (p.Pro72Arg) germline missense variant was identified in the peripheral blood sample. In conclusion, the findings provided new information on genetic aspects that may contribute to OS development, especially in pediatric patients.
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