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Genome sequencing identifies a basis for everolimus sensitivity

Gopa Iyer1, Aphrothiti J Hanrahan, Matthew I Milowsky

  • 1Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

Science (New York, N.Y.)
|August 28, 2012
PubMed

Insights

Whole-genome sequencing identified a TSC1 (tuberous sclerosis complex 1) mutation linked to bladder cancer remission with everolimus. This discovery highlights the potential of genetic biomarkers for predicting patient response to targeted cancer therapies.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacogenomics

Background:

  • Cancer drugs can yield significant responses in a small patient subset.
  • Identifying the genetic underpinnings of drug sensitivity is crucial for personalized medicine.

Purpose of the Study:

  • To investigate the genetic basis for a durable remission in metastatic bladder cancer.
  • To explore the utility of whole-genome sequencing in identifying biomarkers for targeted cancer drug sensitivity.

Main Methods:

  • Whole-genome sequencing was performed on a patient with metastatic bladder cancer achieving remission with everolimus.
  • Targeted sequencing was used to analyze TSC1 (tuberous sclerosis complex 1) mutations in additional bladder cancer samples.

Main Results:

  • A loss-of-function mutation in TSC1, a regulator of the mTOR pathway, was identified in the patient.
  • TSC1 mutations were found in approximately 8% of 109 bladder cancer patients and correlated with everolimus sensitivity.

Conclusions:

  • Whole-genome sequencing can identify previously unrecognized biomarkers for drug sensitivity in a clinical setting.
  • TSC1 mutations may serve as a predictive biomarker for everolimus response in bladder cancer patients.

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