Jeffrey S. Buguliskis Ph.D. Technical Editor Genetic Engineering & Biotechnology News

From Cancer Genome Mutational Profiling, to Epigenetics and Immunotherapy, to One of The Hottest Topics in Life Sciences: CRISPR

PHILADELPHIA—The opening plenary session at the annual AACR meeting saw a collection of researchers studying various aspects of cancer research, come together to collectively address the overall topic of what lies ahead for genomics within the cancer researcher realm.

The presentations touched on a number of topics, from cancer genome mutational profiling, to epigenetics and immunotherapy, to one of the hottest topics in life sciences: CRISPR. After the plethora of data was presented and the excellent talks finished a few points stood out as being important drivers to the future of the field.

Michael Stratton, Ph.D., director of the Wellcome Trust Sanger Institute, kicked off the plenary session by presenting fascinating data describing technology he and his colleagues utilized to obtain mutational profiles for genomes from an array of cancers. Specifically, the researchers profiled whole exome sequencing data from over 12,000 patients that represented 40 distinct cancer types. Dr. Stratton and his team looked for potential patterns that shed insight into the initiation or driver events underlying tumor cell proliferation.

The research team utilized a very interesting method in order to analyze such large amounts of data for their study. They employed the use of non-negative matrix factorization algorithms, which breaks large datasets into small discreet matrices for easier processing. This process is often used by facial recognition software that divides an image of an individual’s face up into to a multitude of smaller pieces, searching for patterns in the milieu.

Once the Sanger team sifted through their mutational analysis data they observed that there were 13 mutational signatures that contributed to the formation of breast cancer. From these signatures the investigators surmised that the APOBEC gene plays a large role in the mutational profiles that they were observing, APOBEC is an mRNA editing enzyme known to have a role in the mutagenesis process for various cancers.   

The presentations continued with Tyler Jacks, Ph.D., director of the Koch Institute for Integrative Cancer Research at MIT, taking the stage and beginning his presentation as many scientists often do, by describing where his research began and how it has taken shape over the years. One aspect of Dr. Jacks’ research was to understand how the immune system controls tumor suppression. He described the classical mechanisms of generating transgenic mice that had various immune cell genes under the control of inducible gene regulators. Dr. Jacks mentioned that while this methodology was sound and provided ample data, it was also costly and could take between two to three years to develop the mice in order to study only a very small number of genes that may be involved in tumor suppression.

A slide was than flashed up displaying ominous storm clouds while Dr. Jacks stated that several years ago this represented the mood of many researchers as they looked toward the future. His next slide than showed a celestial break in the storm clouds with sunlight pouring through when Dr. Jacks announced in a moment of levity that “CRISPR was delivered unto us and it was good!”

Dr. Jacks is certainly not alone in his feelings about the much touted gene editing technology as 1,300 papers have been published in the three years since the enzymes were first described as genome editing tools. Dr. Jacks went on to describe how his laboratory, using CRISPR technology, was able to generate mice with both gain and loss of function mutations within T cells of mice, in order to study their role in tumor suppression. Furthermore, he stated that his team was able to generate data in six months what would have taken them normally five to six years and ending his presentation stating that “If you’re getting the feeling that CRISPR is everywhere in cancer researcher, you would be right.”

One of the remaining key points central to opening session and a topic that is forefront in the mind of many cancer researchers is epigenetics. Stephen Baylin, Ph.D., deputy director of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, tried to instill the audience that while the theme of the session was the genome and beyond, epigenetics is equally above the genome as it is beyond—referring to the regulatory control epigenetics exerts over gene expression. Furthermore, Dr. Baylin, using language suited for the tech savvy generation of young scientists in attendance, described epigenetics as the “software for the hard drive of DNA.”

Dr. Baylin discussed in great detail his work on abnormal hyper-and hypomethylated of promoter regions associated with the loss of important tumor suppressor gene expression during tumor progression. He ended his discussion with the notion that “mining the epigenome is going to have tremendous translational ramifications for the future.”

The 106th annual AACR meeting couldn’t have begun in a finer fashion, with excellent discussions of what lies ahead falling on the ears of the next generation of scientists who will transition cancer research into the beyond.

Continue reading GEN’s related coverage of the 2015 AACR Annual Meeting

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