As precision oncology continues to expand, so does the ability to use less-toxic targeted therapies. James Chen, MD, assistant professor of biomedical informatics and assistant professor of internal medicine at the division of medical oncology at Ohio State University in Columbus, described his work with genomics in cancer care and the challenges in precision medicine at the 43rd Annual Congress in Washington, DC.

During his presentation, Chen covered case examples using genomics for more accurate diagnosis and the types of biomarkers used in precision medicine.

Chen cited three take-home points:

  • Precision medicine can help clarify tumor diagnoses.
  • Precision medicine can guide treatment selection.
  • Precision medicine results are dependent on the testing and subsequent analysis performed.

In precision medicine, no two patients are viewed the same, no two diseases are the same, and similar treatments in similar patients can lead to completely different outcomes. When treating cancer, Chen noted that he sees no “average patient”; some treatments might work for some patients, but others might not have the same result.

Targeted therapies have revolutionized cancer care, and precision medicine drugs becoming the standard in cancer treatment, Chen said.

“Right drug, right target. To pick the right drug, you need to figure out what the target is,” Chen said.

The BRAF V600E mutation in melanoma or EGFR‐mutated tumors in lung cancer are examples of the strides in targeted therapies.

“These are tried and true targets—this was not always the case,” Chen said.

Unfortunately, standard molecular tumor tests available can miss cancerous changes; because of this, the right precision medicine directed therapy could be missed, Chen warned.

Precision medicine genomic tests are different, and current genomic marker assessment falls into four types (see Table 1). At face value, doing a type 4 test with full genome sequencing would in theory cover all bases, but Chen said using this method is not always possible.

“It is very expensive right now. The prices have come down dramatically, but if we did this on every patient—that’s a lot of money,” he said.

Type 1 profiling tests are most commonly used, and include immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR). IHC can show which antibodies are needed against the aberrant protein. With FISH, “It’s going to go in there and find the part of DNA that you’re interested in,” but you must know what you are looking for, Chen said. PCR works similarly to FISH, but instead amplifies the part of DNA and makes it big.

Type 2 testing can help sequence hot spot panels and find mutations and changes, and “you don’t need to know the mutation or change ahead of time, but you need to know the particular spot,” Chen said.

For type 3 testing, a more comprehensive genomic profiling, the entire exon is sequenced. This allows clinicians to identify all base substitutions, all insertions and deletions, all copy number alterations, and select rearrangements.

Type 4 testing, although costly, can sequence:

  • All base substitutions
  • All insertions/deletions
  • All copy number alterations
  • All rearrangements
  • All binding region alterations

“Just having the DNA sequence isn’t telling you anything. Just knowing it’s mutated is not enough; we need to know if it’s doing something,” Chen said.

He added that data on DNA isn’t useful unless it has:

  • Quality control: Are the data any good?
  • Calling: Is this really a change?
  • Annotation: Is this change going to cause cancer or change the function of the gene?

It’s important to know what you’re looking for in these mutations, no matter which test is chosen.

“You can test all you want, but know what you’re ordering and why you’re ordering it,” Chen said. “Not all tests are the same. You have to think a little about the context.”

Table 1. Types of Genetic Tests



Type 1 Tests: Single Gene Markers

  • Number of genes: one known gene
  • Techniques: IHC, PCR, and FISH
  • Which genes: commonly altered genes
  • Limitations: misses rare and novel alterations

Type 2 Tests: Hot‐Spot NGS Panels

  • Number of genes: multiple parts of multiple genes
  • Techniques: next-generation sequencing
  • Which genes: commonly altered genes
  • Limitations: misses other type of alterations, misses rare and novel alterations

Type 3 Tests: Comprehensive Genomic Panels

  • Number of genes: multiple; entire coding region of genes known to be somatically altered
  • Technique: next-generation sequencing
  • Which genes: commonly altered genes
  • Limitations: doesn’t typically assay intronic areas

Type 4 Test: Full Genome Sequencing

  • Number of genes: all genes, coding and non‐coding regions
  • Technique: next-generation sequencing
  • Which genes: all genes
  • Limitations: costly