Analysis of Our Molecular Profiling Results in Patients with Relapsed / Refractory Tumors

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Ataseven E. , Biray Avcı Ç. , Önen Göktepe Ş. Ş. , Selvi Günel N. , Göde S. , Bağca B. G. , ...More

SIOP 2021, 21 - 24 October 2021, vol.68, pp.513

  • Publication Type: Conference Paper / Summary Text
  • Volume: 68
  • Page Numbers: pp.513


Background and Aims: Today, by determining specific genetic changes in tumors, it is possible to give individualized treatment specific to each patient. However, the effectiveness of these treatments in childhood cancers is still controversial. Here, we present the genetic changes detected in the tumor tissues of relapsed / refractory patients in our clinic and the treatments initiated due to these genetic changes. Methods: DNA isolation was performed from paraffin-embedded tumor tissues of the cases. The appropriate samples were subjected to clonal amplification and sequencing, and next-generation sequencing was performed. The pathogenicity of the determined variant and copy number changes (CNV) was evaluated. Results: A total of 25 patients evaluated. There were 13 females(52%) and 12 males(48%). Median age was 6,5 years(2,5- 16,5 years). 16 of those were dignosed as CNS tumor consisting of medulloblastoma(n=2), low grade astrocytoma(n=4), high grade astrositoma(n=8), ependymoma(n=1), ATRT(n=1). The remaining 9 patients were diagnosed as rabdomyosarcoma(n=5), Wilms tumor (n=1), hepatoblastoma(n=1), Ewing sarcoma(n=1), alveolar soft part sarcoma(n=1). Pathogenic and/or possible CNV was detected in seven patients with CNS tumors. Deletion of NF-1was determined in 3 patients. Significant variants such as SMARCA4(n=3), ARID1A(n=3), KMT2D(n=2), MSH(n=2), EGFR(n=1), FGFR3(n=1), MTOR(n=1) mutations were identified. Pathogenic and/or possible pathogenic variants and/or CNV were defined in 6 patients without CNS tumor. NF deletion(n=3), and MET amplification(n=1) were specified. Significant variants such as PTCH1(n=2), PIK3CA(n=1), SMARCA4(n=1), KRAS(n=1), RAC(n=1), MAX(n=1) were determined. One of the patients diagnosed as relapse rhabdomyosarcoma with KRAS and NF-1 mutation received trametinib, whereas anaplastic astrocytoma with EGFR mutation was treated afatinib. Crizotinib was given to the relapse rhabdomyosarcoma with MET amplification. The patient with Wilms tumor, including RAC and MAX mutation, was medicated with regorafenib. Conclusions: In evaluating tumor specimens of patients, numerous tumor mutations were recognized. However, cause of the lack and limitations of the studies about targeted therapies in children, each patient could not receive a specific drug. The treatment’s validity and benefit can only be discussed with further studies.