Columbia Technology Ventures

Non-invasive method for detection of cancer methylomes

This technology is a method of isolating polynucleotides from cell-free non-invasive bodily samples and sequencing them to detect methylated DNA to identify early tumors.

Unmet Need: Non-invasive methods for early tumor identification and characterization

Current methods to detect and diagnose tumors rely on invasive surgery to acquire tissue specimens, which often only catches tumors in advanced stages. The presence of plasma cell free DNA (cfDNA) released from the tumor into the blood stream has been identified as a potential biomarker for tumors and can be acquired using non-invasive methods. However, the use of plasma cfDNA as a biomarker for tumor identification has been hindered by the low abundance of cfDNA released by tumors. Currently, few methods of cfDNA profiling that are sensitive enough to detect low levels of tumor-specific cfDNA.

The Technology: Sensitive methylome profiling of tumor derived plasma DNA

This technology isolates cell free DNA (cfDNA) from polynucleotides found in plasma, serum, urine, saliva, and other bodily excretions by mixing them with sequencing primers and DNA polymerase. Methylated DNA is then purified through immunoprecipitation using antibodies targeting 5-methylcytosine (5mC), PCR amplified, and deep sequenced. The major advance of this method is that it can analyze both DNA methylation and hemi-methylation, the latter of which occurs in 10% CpG dinucleotides in human genome. Therefore, this method can be used to identify both the presence of tumors and the tumor cell-type-of-origin based on both DNA methylation and hemi-methylation patterns, which increase the sensitivity and accuracy of tumor detection

This technology has been validated with human plasma samples and tumor samples.

Applications:

  • Diagnostic assay for early detection of cancer including central nervous system (CNS) cancer, colon cancer, liver cancer and pancreatic cancer
  • Diagnostic assay for cancer cell-of-origin identification
  • Selection of optimal therapeutic treatment based on tumor methylome
  • Research tool for analysis of tumor methylome

Advantages:

  • DNA methylation detected with high specificity
  • Low amount of input DNA required
  • Non-invasive collection from blood, plasma, serum, urine, saliva, mucosal excretions, sputum, stool or tears.
  • Can be adapted to profile other epigenetic marks
  • Simplified sequencing library preparation

Lead Inventor:

Zhiguo Zhang, Ph.D.

Patent Information:

Patent Pending([WO/2022/187867] (https://patents.google.com/patent/WO2022187867A1/en?oq=PCT%2fUS2022%2f070%2c998))

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