Whole Exome Sequencing Versus RNA Sequencing

Assessing Risk & Developing Precision Therapies for Cancer Patients Through Whole Exome & RNA Sequencing

Cancer is a highly complex set of diseases, and understanding its causes and progression in individuals requires a wide array of considerations and research approaches. Everything from environmental factors and exposure to certain infections to dietary and physical activity habits can contribute to the development of certain cancers. However, cancer is ultimately a genetic disease. As such, genetic sequencing technologies, such as whole exome and RNA sequencing, have a key role in helping researchers understand why individuals develop certain types of cancer. Armed with this vital knowledge, scientists can then develop next-generation, personalized cancer therapies.


Although genetic sequencing can be traced back to the 1970s, only in the past two decades has this technology gained traction as a powerful tool in the fight against cancer. An incredible advancement was made with the Human Genome Project, which was completed in 2003 and represented the first comprehensive mapping of the 3.2 billion base pairs that make up the human genome.

This groundbreaking work gave rise to rapid advancements in genetic sequencing technologies, techniques, and applications. With regard to cancer, sequencing tumors provides invaluable insights, laying the groundwork for more effective treatments that are targeted to individuals’ genetic profiles. Additionally, further advancements have been made with the development of RNA sequencing and whole exome sequencing. As a leading oncology-focused bioinformatics company, M2GEN leverages both of these techniques, along with germline sequencing and longitudinal clinical data, to create robust in silico patient profiles.

The Importance of Whole Exome Sequencing and RNA sequencing for Cancer Research

Whole exome sequencing is a time- and cost-intensive process, which has driven the development of more targeted next-generation sequencing techniques. Whole exome and RNA sequencing offer a solution to focus specifically on the features of the human genome that most critically impact the development and progression of various cancers in individual patients and can provide insights into potentially actionable targets for treating their disease.

What Is Whole Exome Sequencing?

This technique is used for sequencing the protein-coding regions of an individual's genetic profile. Each protein-coding segment of a gene is called an exon, and in combination, all exons within the genome are known as the exome. Therefore, whole exome sequencing involves deciphering the genetic code that is responsible for all coding proteins in the body and identifying if errors in a gene may have occurred. Interestingly, the exome only makes up less than 2% of the total genome, translating to roughly 30 million base pairs. As a result, whole exome sequencing is much more precise, time efficient, and cost efficient than whole genome sequencing.

Of course, efficiency is not the primary reason for using whole exome sequencing in cancer research. Most genetic diseases, including cancers, can be traced back to exon mutations. By focusing on this portion of the genome, whole exome sequencing can provide insight into genetic biomarkers that indicate an elevated risk for the development of specific types of cancer. Additionally, better understanding these disease-causing mutations provides a rich vein of data for researchers to explore and leverage in creating treatments that are targeted to individual genetic profiles.

What Is RNA Sequencing?

RNA sequencing is a next-generation transcriptome profiling technique. The transcriptome, which is comprised of all of the messenger RNA (mRNA) expressed within an individual cell or tissue type, reveals which genes are actively turned on or off and can expose irregular patterns of expression that may indicate an underlying problem in the DNA.

RNA sequencing offers great insight into gene expression profiles that provide scientists with detailed information about which genes and pathways may be inappropriately up- or down-regulated within a patient’s tumor. Taken hand-in-hand with whole exome sequencing, this allows researchers to identify how the changes in expression relate to underlying genetic anomalies, and ultimately which genetic changes drive cancer development or progression. Additionally, this technique can aid in the discovery of novel cancer biomarkers and pathways that may be targetable by new or existing therapies.

Key Differences Between Whole Exome & RNA Sequencing

Because disease-causing genetic mutations primarily occur within the exome, cancer researchers are justified in focusing on this region of patient genetic profiles. Even RNA sequencing is primarily used to examine transcriptome data derived from exons. However, there are important distinctions between these two sequencing techniques besides the fact that one is sequencing DNA and the other is sequencing mRNAs. For example, though RNA sequencing largely yields data related to the exome, it can be used to identify irregularities stemming from regions beyond just exons, such as introns and gene rearrangements resulting in fusion proteins that would not easily be recognized by whole exome sequencing alone. Additionally, RNA levels for various genes fluctuate depending on the individual or even the type of tissue. Monitoring these fluctuations can shed light on how various gene expression levels relate to tumor progression and response to treatments.

Bringing Cancer into Focus

At M2GEN, we are helping to unlock the full potential of whole exome and RNA sequencing for cancer research and development of precision therapies. By pairing insights derived from these techniques with patients’ longitudinal clinical information, we provide our research partners with access to first-in-kind platforms containing robust, structured, and contextualized data. Our ORIEN AVATAR® Program is a perfect example. AVATAR consists of comprehensive, in silico genotypic and phenotypic profiles of consenting cancer patients. Utilizing next-generation sequencing (NGS), our solutions include data derived from paired tumor and germline whole exome sequencing and tumor RNA sequencing. This enables the creation of advanced cohorts that can be used to closely examine nuanced aspects of various types of cancers, ranging from the presence of specific biomarkers and mutations to genetic factors affecting treatment progressions and recurrences.

To learn more about how our research partners are leveraging M2GEN’s unparalleled genomic and longitudinal clinical data pipeline in the fight against cancer, contact us today.