Dataset Information

Clinical Relevance of Genomic Changes in Recurrent Pediatric Solid Tumors.

ABSTRACT:

Purpose

Relapsed/refractory pediatric cancers show poor prognosis; however, their genomic patterns remain unknown. To investigate the genetic mechanisms of tumor relapse and therapy resistance, we characterized genomic alterations in diagnostic and relapsed lesions in patients with relapsed/refractory pediatric solid tumors using targeted deep sequencing.

Patients and methods

A targeted sequencing panel covering the exons of 381 cancer genes was used to characterize 19 paired diagnostic and relapsed samples from patients with relapsed/refractory pediatric solid tumors.

Results

The mean coverage for all samples was 930.6× (SD = 213.8). Among the 381 genes, 173 single nucleotide variations (SNVs)/insertion-deletions (InDels), 100 copy number alterations, and 1 structural variation were detected. A total of 72.6% of SNVs in primary tumors were also found in recurrent lesions, and 27.2% of SNVs in recurrent tumors had newly occurred. Among SNVs/InDels detected only in recurrent lesions, 71% had a low variant allele fraction (<10%). Patients were classified into three categories based on the mutation patterns after cancer treatment. A significant association between the major mutation patterns and clinical outcome was observed. Patients whose relapsed tumor had fewer mutations than the diagnostic sample tended to be older, had longer progression-free survival, and achieved complete remission after relapse. Contrastingly, patients whose genetic profile only had concordant mutations without any change had the worst outcome.

Conclusions

We characterized genomic changes in recurrent pediatric solid tumors. These findings could help to understand the biology of relapsed childhood cancer and to develop personalized treatment based on their genetic profile.

SUBMITTER: Lee B

PROVIDER: S-EPMC6134157 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical Relevance of Genomic Changes in Recurrent Pediatric Solid Tumors.

Lee Boram B Lee Ji Won JW Shim Joon Ho JH Joung Je-Gun JG Yun Jae Won JW Bae Joon Seol JS Shin Hyun-Tae HT Sung Ki Woong KW Park Woong-Yang WY

Translational oncology 20180911 6

<h4>Purpose</h4>Relapsed/refractory pediatric cancers show poor prognosis; however, their genomic patterns remain unknown. To investigate the genetic mechanisms of tumor relapse and therapy resistance, we characterized genomic alterations in diagnostic and relapsed lesions in patients with relapsed/refractory pediatric solid tumors using targeted deep sequencing.<h4>Patients and methods</h4>A targeted sequencing panel covering the exons of 381 cancer genes was used to characterize 19 paired diag ...[more]

PMID: 30216764

Similar Datasets

Project description:BACKGROUND: Primitive brain tumors are the leading cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). Most high-grade glioma-derived oncospheres (10/12) sustained long-term self-renewal akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumors. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P?=?0.05, chi-square test). Survival analysis of the cohort showed an association between isolation of cells with long-term self-renewal abilities and a higher patient mortality rate (P?=?0.013, log-rank test). Sampling of low- and high-grade glioma cultures showed that self-renewing cells forming oncospheres shared a molecular profile comprising embryonic and neural stem cell markers. Further characterization performed on subsets of high-grade gliomas and one low-grade glioma culture showed combination of this profile with mesenchymal markers, the radio-chemoresistance of the cells and the formation of aggressive tumors after intracerebral grafting. CONCLUSIONS/SIGNIFICANCE: In brain tumors affecting adult patients, TSCs have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors.

Dataset Information

Clinical Relevance of Genomic Changes in Recurrent Pediatric Solid Tumors.

Purpose

Patients and methods

Results

Conclusions

Publications

Clinical Relevance of Genomic Changes in Recurrent Pediatric Solid Tumors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets