Whole Exome- and mRNA-Sequencing of an ATRT Case Reveals Few Somatic Mutations and Several Deregulated Signalling Pathways in the Context of SMARCB1 Deficiency
المؤلفون المشاركون
Sandgren, Johanna
Holm, Stefan
Marino, Ana Maria
Asmundsson, Jurate
Grillner, Pernilla
Díaz de Ståhl, Teresita
Nistér, Monica
المصدر
العدد
المجلد 2015، العدد 2015 (31 ديسمبر/كانون الأول 2015)، ص ص. 1-12، 12ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2015-08-12
دولة النشر
مصر
عدد الصفحات
12
التخصصات الرئيسية
الملخص EN
Background.
AT/RTs are rare aggressive brain tumours, mainly affecting young children.
Most cases present with genetic inactivation of SMARCB1, a core member of the SWI/SNF chromatin-remodeling complex.
We have performed whole exome- and mRNA-sequencing on an early onset AT/RT case for detection of genetic events potentially contributing to the disease.
Results.
A de novo germline variant in SMARCB1, c.601C>T p.Arg201∗, in combination with somatic deletion of the healthy allele is likely the major tumour causing event.
Only seven somatic small scale mutations were discovered (hitting SEPT03, H2BFM, ZIC4, HIST2H2AB, ZIK1, KRTAP6-3, and IFNA8).
All were found with subclonal allele frequencies (range 5.7–17%) and none were expressed.
However, besides SMARCB1, candidate genes affected by predicted damaging germline variants that were expressed were detected (KDM5C, NUMA1, and PCM1).
Analysis of differently expressed genes revealed many dysregulated pathways in the tumour, such as cell cycle, CXCR4 pathway, GPCR-signalling, and neuronal system.
FGFR1, CXCR4, and MDK were upregulated and may represent possible drug targets.
Conclusion.
The loss of SMARCB1 function leads to AT/RT development and deregulated genes and pathways.
Additional predisposing events may however contribute.
Studies utilizing NGS technologies in larger cohorts will probably identify recurrent genetic and epigenetic alterations and molecular subgroups with implications for clinical practice and development of targeted therapies.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Sandgren, Johanna& Holm, Stefan& Marino, Ana Maria& Asmundsson, Jurate& Grillner, Pernilla& Nistér, Monica…[et al.]. 2015. Whole Exome- and mRNA-Sequencing of an ATRT Case Reveals Few Somatic Mutations and Several Deregulated Signalling Pathways in the Context of SMARCB1 Deficiency. BioMed Research International،Vol. 2015, no. 2015, pp.1-12.
https://search.emarefa.net/detail/BIM-1057050
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Sandgren, Johanna…[et al.]. Whole Exome- and mRNA-Sequencing of an ATRT Case Reveals Few Somatic Mutations and Several Deregulated Signalling Pathways in the Context of SMARCB1 Deficiency. BioMed Research International No. 2015 (2015), pp.1-12.
https://search.emarefa.net/detail/BIM-1057050
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Sandgren, Johanna& Holm, Stefan& Marino, Ana Maria& Asmundsson, Jurate& Grillner, Pernilla& Nistér, Monica…[et al.]. Whole Exome- and mRNA-Sequencing of an ATRT Case Reveals Few Somatic Mutations and Several Deregulated Signalling Pathways in the Context of SMARCB1 Deficiency. BioMed Research International. 2015. Vol. 2015, no. 2015, pp.1-12.
https://search.emarefa.net/detail/BIM-1057050
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1057050
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر