Whole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance
| العنوان: | Whole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance |
|---|---|
| المؤلفون: | Gustaf Ljungman, Per Kogner, Tommy Martinsson, Angela Martinez-Monleon, Caroline Björklund, Torben Ek, Mathias Johansson, Rose-Marie Sjöberg, Susanne Fransson |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020) Scientific Reports |
| بيانات النشر: | Nature Portfolio, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, Male, DNA Copy Number Variations, DNA repair, Somatic cell, Science, Biology, Germline, Article, Neuroblastoma, medicine, Biomarkers, Tumor, Genetics, Humans, Gene Regulatory Networks, CHEK2, Aged, Cancer, Medicinsk genetik, Whole genome sequencing, Aged, 80 and over, Cancer och onkologi, Multidisciplinary, Whole Genome Sequencing, Telomere Homeostasis, Middle Aged, Telomere, medicine.disease, Prognosis, Gene Expression Regulation, Neoplastic, Oncology, Cancer and Oncology, Mutation, Cancer research, Disease Progression, Medicine, Female, Neoplasm Recurrence, Local, Medical Genetics |
| الوصف: | Neuroblastoma is the most common and deadly childhood tumor. Relapsed or refractory neuroblastoma has a very poor prognosis despite recent treatment advances. To investigate genomic alterations associated with relapse and therapy resistance, whole-genome sequencing was performed on diagnostic and relapsed lesions together with constitutional DNA from seven children. Sequencing of relapsed tumors indicates somatic alterations in diverse genes, including those involved in RAS-MAPK signaling, promoting cell cycle progression or function in telomere maintenance and immortalization. Among recurrent alterations, CCND1-gain, TERT-rearrangements, and point mutations in POLR2A, CDK5RAP, and MUC16 were shown in ≥ 2 individuals. Our cohort contained examples of converging genomic alterations in primary-relapse tumor pairs, indicating dependencies related to specific genetic lesions. We also detected rare genetic germline variants in DNA repair genes (e.g., BARD1, BRCA2, CHEK2, and WRN) that might cooperate with somatically acquired variants in these patients with highly aggressive recurrent neuroblastoma. Our data indicate the importance of monitoring recurrent neuroblastoma through sequential genomic characterization and that new therapeutic approaches combining the targeting of MAPK signaling, cell cycle progression, and telomere activity are required for this challenging patient group. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9c14a0094aa5e197dd67701aeed07c2cTest https://doaj.org/article/040e279adcf3445389b188aed659660dTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9c14a0094aa5e197dd67701aeed07c2c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
|---|