Cancer genomics testing

What is cancer genomics?

Cancer cells are not similar to normal cells. They acquire mutations. These mutations make them different. Most of these mutations give cancer cells power of unlimited growth, resulting in removal of normal functioning cells of the tissues, and subsequently leading to organ failure. Some mutations are repetitive, means they appear in cancer patients very frequently. Some mutations are rare, which means it appears rarely. Regardless, cancer cells have multiple gene mutations. The analysis and study of the cancer gene mutations and relating them to better treatment approaches with improved outcome is known as cancer genomics.

How are cancer mutations identified?

Cancer mutations are identified by collecting the cancer cells from resected tumors and then sequencing the genome of these cells using a technique called NextGen sequencing. Gene sequencing information from thousands of different cancer patients have generated a wealth of information. We have learned a lot about how mutations can alter the outcomes of cancer treatments.

Loose cancer cells circulating in the blood can be collected and the DNA can be sequenced. This process is called liquid biopsy. Liquid biopsies are increasingly becoming a tool to predict the progression of caner or to estimate residual cancer. Cancer cells come loose from the tumor itself and enters into the blood stream. This is how they metastasize and enter into another organ.

What can be done with the information generated from cancer genomics testing?

Below I will describe a few examples to describe this.

1. Targeted therapy in lung cancer

The molecular profiling of lung cancers has uncovered several mutated proteins. They are shown below.

EGFR – mutated in 52% of never-smokers, 15% former smokers, 6% current smokers

KRAS – predominant in smokers or former smokers

ALK – predominant in non-smokers {fusions in 3%-7% of the non-small cell lung cancer (NSCLC)}

HER2 – predominant in non-smokers (mutation present in 2% of the tumors)

BRAF – predominant in smokers or former smokers (mutation present in 1% - 3% of the tumors)

PI3KCA – mutation present in 2% of the tumors

AKT1 – mutation present in 1% of the tumors

MAP2K1 or MEK1 – mutation present in 1% of the non-small cell lung cancer (NSCLC)

MET – amplification of this gene is associated with secondary resistance to EGFR tyrosine kinase inhibitors

Lets talk about EGFR mutations. EGFR stands for epidermal growth factor receptor. EGFR mutations such as exon 19 deletion or exon 21 L858R mutation can be treated with medications such as Afatinib Dimaleate, which significantly increases the median overall survival when compared to cisplatin treatment in NSCLC patients. In addition, Atezolizumab, a humanized monoclonal antibody against PD-L1 shows significantly improved overall survival in patients with EGFR mutations.

2. Liquid biopsy results

Here we are going to talk about a different scenario. A liquid biopsy result from a breast cancer patient shows several mutations identified from floating cancer cells. Let's suppose the one of the mutations is TP53 R273C. The doctor's office or the lab will report that this mutation is non-actionable, which means, there can nothing be done with this information treatment wise. However, they may be correct on the treatment part, but there is a lot that a patient can learn from this mutation status. A patient can learn how this TP53 mutation alters the survival outcome. Below is a survival curve generated by analyzing 7469 breast cancer patients. The red line shows patient survival with this particular TP53 mutation. The analysis shows that patients with TP53 mutation/s survive less longer compared to patients without mutated TP53.

Median Months Overall (95% CI)

Altered group (TP53 mutated) 126.47 (111.97 - 144.67)

Unaltered group 169.23 (160.33 - 179.10)

But then, with the subtype of breast cancers, this outcome may be different. Majority of the breast cancer patients have breast invasive ductal carcinoma. With this particular type of breast cancer, TP53 mutations may result in better overall survival with proper treatment, when compared to the not mutated group. Below is a survival graph for the breast invasive ductal carcinoma patients.

Although not statistically significant, the trend shows that the unaltered group survives less longer compared to the TP53 mutated group. Now when the total number of patients in the database will increase, this result will be statistically significant.

Hopefully, this little section is going to get the readers interested enough to learn more about cancer genomics and testing. For questions, please email at


Author: Anirban Mukherjee, PhD

Research Scientist

The Dell Pediatric Research Institute

The Dell Medical School

College of Pharmacy, The University of Texas at Austin

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