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Targeted next-generation DNA sequencing identifies Notch signaling pathway mutation as a predictor of radiation

Seung Hyuck Jeon1, Eui Kyu Chie1,2, Yi-Jun Kim1

  • 1Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.

International Journal of Radiation Biology
|September 17, 2019
PubMed

Insights

Somatic mutations in the Notch signaling pathway may predict tumor radiosensitivity. This finding could advance personalized radiotherapy by identifying patients likely to respond to radiation treatment.

Area of Science:

  • Oncology
  • Genetics
  • Radiotherapy

Background:

  • Understanding tumor somatic mutations and their link to radiation response is crucial for personalized radiotherapy.
  • Targeted next-generation DNA sequencing offers a method to identify genetic factors influencing treatment outcomes.

Purpose of the Study:

  • To identify specific genes or molecular pathways associated with tumor response to radiotherapy.
  • To investigate the association between somatic mutations and clinical outcomes in patients undergoing radiotherapy.

Main Methods:

  • Targeted next-generation DNA sequencing of 148 cancer-related genes in 55 solid tumor patients.
  • Analysis of mutations in 39 molecular pathways and their correlation with radiation response, defined by remission duration.
  • Biologically effective dose (BED) and concurrent chemotherapy were assessed as potential influencing factors.

Main Results:

  • No single gene mutation was significantly correlated with radiation response.
  • Mutations in the Notch signaling pathway showed a trend towards association with radiosensitivity (adjusted p=0.094).
  • Both Biologically Effective Dose (BED) and Notch signaling pathway mutations were independently associated with radiation response in logistic regression analysis.

Conclusions:

  • Somatic mutations within the Notch signaling pathway may play a role in determining tumor sensitivity to radiation therapy.
  • These preliminary findings warrant validation in larger, more homogeneous patient cohorts to confirm the association and clinical utility.
Keywords:
Radiotherapymolecular pathwaynext-generation sequencingradiogenomicsradiosensitivitytargeted sequencing

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