Sequencing a cancer patient’s genome can be a brilliant diagnostic tool because it helps doctors select the best treatment for them, researchers from Washington University School of Medicine in St. Louis wrote in JAMA (Journal of the American Medical Association) – they carried out two studies.

The First Study – a 39-year old female patient with AML (acute myeloid leukemia) had her genome sequenced, which revealed a novel genetic error, resulting in a change of treatment. Rather than the initially recommended stem cell transplant, she received targeted chemotherapy. All the signs and symptoms of her cancer have now disappeared – she is now in remission.

Peter Westervelt, MD, PhD, the patient’s oncologist, said:

“We didn’t want to go through with a stem cell transplant unless we were absolutely certain she needed it. It’s a very rigorous therapy, with a significant risk of mortality and long-term complications. Sequencing the genome of the patient’s leukemia cells offered the opportunity to resolve this dilemma in ‘real time’ and allowed us to make the correct call in recommending further therapy.”

The Second Study – the genome of a deceased 42-year-old female patient who had developed breast and ovarian cancer and then leukemia was sequenced. The investigators detected a new mutation in a gene known to considerably raise the risk of cancer. Her family was told and was subsequently advised to receive genetic counseling – the patient’s three offspring have a significantly high risk of developing cancer early on in life.

Even though the patient’s family history showed just one relative on the mother’s side who had had cancer – not a strong indicator of an inherited disposition – the doctors suspected there may have been a genetic susceptibility for cancer risk.

Lead author and oncologist Daniel Link, MD, the Alan A. and Edith L. Wolff, said:

“We see cases like this all the time. A patient develops one or two primary cancers at a young age, and there’s no significant family history of cancer. The red light goes on; we know there has to be a reason why.”

Doctors usually carry out commercial testing for BRCA1 and BRAC2 mutations in females who develop ovarian or breast cancer at an early age, as occurred with this patient.

Link said:

“But this patient had three children. If we could find the mutation that increased her cancer risk, it would be important for her family to know.”

Boris Pasche, MD, PhD, of the University of Alabama in Birmingham, and Devin Absher, PhD, of the HudsonAlpha Institute for Biotechnology in Alabama, in an Accompanying Editorial, wrote:

“These cases of personalized genomic medicine are just some of the first examples of what will likely be commonplace in the near future.”

Richard K. Wilson, PhD, director of Washington University’s Genome Institute, wrote:

“We are beginning to see how genome sequencing can make a real difference in the lives of cancer patients and their families. Both studies underscore the value of whole-genome sequencing as a diagnostic tool. We could not have identified these mutations using conventional tests or targeted sequencing approaches because they involved unexpected structural changes to the DNA, which can only be found by looking across the entire genome.”

Thanks to scientific and medical advances, we can now sequence cancer patients’ genomes rapidly and at a more affordable cost, the authors added, something that was not possible until recently.

Even though genome sequencing is cheaper today than it was, it is still too costly to consider routine sequencing for all cancer patients. We still need to understand the full extent of the genetic changes that cause cancer to occur. However, these select cases give us a glimpse of how such personalized sequencing can alter the way physicians diagnose and treat cancer, as well as how cancer patients’ families can be warned of inherited diseases.

It took six weeks to complete the sequencing of the first patient’s genome at a cost of $20,000 per genome – a total cost of $40,000. The researchers say that as technology advances, sequencing times and costs will be reduced.

Co-author Timothy Ley, MD, and Rosalind B. Apple, wrote:

“Whole-genome sequencing is the most powerful diagnostic tool we’ve ever had to define all the mutations in the genome of a cancer patient. We no longer have to rely on techniques where we’re guessing what could be wrong. Now, we can find all the genetic mutations that contributed to a patient’s cancer. As we move forward, we think this will lead to more opportunities to improve the care of patients and their families.”

So far, Wilson, Ley and team have sequenced over 300 cancer patients and their tumors. They have led the way in whole-genome sequencing of cancer patients’ DNA to identify genetic mutations which are the root cause of the disease.

‘Identification of a Novel TP53 Cancer Susceptibility Mutation Through Whole-Genome Sequencing of a Patient With Therapy-Related AML”
Daniel C. Link, MD; Laura G. Schuettpelz, MD, PhD; Dong Shen, MD, PhD; Jinling Wang, MD; Matthew J. Walter, MD; Shashikant Kulkarni, PhD; Jacqueline E. Payton, MD, PhD; Jennifer Ivanovich, MS; Paul J. Goodfellow, PhD; Michelle Le Beau, PhD; Daniel C. Koboldt, MS; David J. Dooling, PhD; Robert S. Fulton, MS; R. Hugh F. Bender, MS; Lucinda L. Fulton, MS; Kimberly D. Delehaunty, BA; Catrina C. Fronick, BS; Elizabeth L. Appelbaum, BA; Heather Schmidt, BS; Rachel Abbott, BS; Michelle O’Laughlin, BS; Ken Chen, PhD; Michael D. McLellan, BS; Nobish Varghese, MS; Rakesh Nagarajan, MD, PhD; Sharon Heath, CCRP; Timothy A. Graubert, MD; Li Ding, PhD; Timothy J. Ley, MD; Gerard P. Zambetti, PhD; Richard K. Wilson, PhD; Elaine R. Mardis, PhD
JAMA. 2011;305(15):1568-1576. doi: 10.1001/jama.2011.473

“Use of Whole-Genome Sequencing to Diagnose a Cryptic Fusion Oncogene”
John S. Welch, MD, PhD; Peter Westervelt, MD, PhD; Li Ding, PhD; David E. Larson, PhD; Jeffery M. Klco, MD, PhD; Shashikant Kulkarni, PhD; John Wallis, PhD; Ken Chen, PhD; Jacqueline E. Payton, MD, PhD; Robert S. Fulton, MS; Joelle Veizer, BS; Heather Schmidt, BS; Tammi L. Vickery, BS; Sharon Heath; Mark A. Watson, MD, PhD; Michael H. Tomasson, MD; Daniel C. Link, MD; Timothy A. Graubert, MD; John F. DiPersio, MD, PhD; Elaine R. Mardis, PhD; Timothy J. Ley, MD; Richard K. Wilson, PhD
JAMA. 2011;305(15):1577-1584. doi: 10.1001/jama.2011.497

Written by Christian Nordqvist