St. Jude Biorepository: A Hope Chest of Cells

Among the most sophisticated worldwide, the St. Jude Biorepository preserves biological samples for use in groundbreaking research.

  

By Maureen Salamon; Photos by Seth Dixon

 
Forceps pick up an icy frozen tissue sample.

Frozen in time: a sample from the St. Jude Biorepository

In the week that Carlos Sepulveda describes as “the craziest of my life,” the college student was diagnosed with a rare form of cancer, underwent three surgeries and embarked on a treatment plan entailing 35 sessions of radiation therapy at St. Jude Children’s Research Hospital.

Four years later, one event from that whirlwind week still stands out to Carlos. He recalls giving consent for samples of his tumor to be collected and stored for research. Even while grappling with a jolting diagnosis and a flood of related details, the young man understood that capturing cells from his tumor—a cancer called liposarcoma—might someday benefit others.

Carlos agreed to contribute both tumor and healthy cells to the St. Jude Biorepository, one of the most sophisticated resources of its kind in the world. Also known as a tissue bank, the facility houses samples dating back more than 40 years.

The Biorepository fuels research into cancer and other diseases. Like a hope chest, this collection of cells is safely tucked away as research techniques increasingly “come of age” to unlock their secrets.

“When I first learned how rare my cancer was, I understood why it was a good research opportunity for St. Jude,” says Carlos, now 25. “It was essentially a no-brainer for me to agree to participate and help other patients.”

A Biological Treasure Trove

Launched informally in the mid-1970s with blood and bone marrow samples from childhood leukemia patients, the St. Jude Biorepository became one of the first five nationwide to be accredited by the College of American Pathologists. The collection now contains more than 500,000 specimens donated by current patients, long-term survivors, participants in St. Jude clinical trials worldwide, and children with non-malignant blood disorders such as sickle cell disease and bone marrow failure syndromes.

Growing at a rate of about 20 percent each year, the bank includes leukemia, brain and solid tumor samples, samples from patients with non-cancer conditions, serum, plasma, DNA, RNA and urine. St. Jude often collects both normal and diseased cells from the same patient, enabling scientists to compare the characteristics, such as genetic features, of each. All research samples are de-identified to ensure patient privacy.

“We collect about 5,000 specimens a month,” says Matt Lear, the Biorepository’s technical director. “That’s fairly significant, given that St. Jude admits between 500 and 600 new patients per year. But most hospitals only see patients a few times in the course of their lifetime, whereas we see fewer patients but see them more often.”  

Matt Lear and Charles Mullighan, MBBS, MD,

Matt Lear (at left) and Charles Mullighan, MBBS, MD, retrieve a tissue sample from the St. Jude Biorepository.

Time is of the Essence

Although a cancer diagnosis is a fraught time for patients and families, it’s also a pivotal point for collecting tissue samples, according to Charles Mullighan, MBBS, MD, medical director of the Biorepository. That’s because researchers need to be able to contrast untreated tissue—taken before therapy begins—with cellular changes occurring after treatment.

More than 95 percent of St. Jude families agree to contribute. 

“Many patients want to enable research that will try to understand the condition better and improve things for themselves or future patients,” Mullighan says. “The culture at St. Jude is geared toward research, and most patients want to participate in that.”

Revolutionary Insights

Which research using Biorepository samples has proven most compelling so far?

“That’s like asking to choose between your children,” Mullighan quips. But there are undeniable standouts, he adds, including many discoveries from the Pediatric Cancer Genome Project and the St. Jude LIFE clinical trial.

The St. Jude LIFE study brings long-term childhood cancer survivors back to campus for regular health screenings throughout adulthood. Scientists recently reported on next-generation gene sequencing conducted on tissue donated by 3,000 such survivors. About 25 percent of survivors who developed second cancers had inherited gene mutations predisposing them to cancer. 

Making Discoveries Possible

Meanwhile, the Pediatric Cancer Genome Project, the world’s most ambitious effort to discover the origins of childhood cancer, teamed St. Jude with Washington University in St. Louis. Researchers compared the complete genomes from both cancerous and normal cells in more than 800 patients. This project identified unexpected genetic changes in many of the most clinically challenging pediatric tumors, such as high-risk acute lymphoblastic leukemia and brain tumors.

Sequencing of matched non-tumor samples from children with cancer also revealed that more than 8 percent of children with cancer have genetic predispositions.

“The Genome Project has been revolutionary,” Mullighan says. “It has provided new tools to analyze cancer genomes, fundamental new understandings of how tumors develop and grow, new diagnostic tests and new therapeutic approaches. A number of these have been rapidly pushed into the clinic.” 

ST. JUDE BIOREPOSITORY

 

Frozen in Time

The logistics of running the Biorepository are immensely complex, from coordinating the efforts of an expanding team to the technical demands of preserving and rationing samples for multiple types of research.

In the last nine years, the Biorepository’s roster of lab technicians has doubled to six, while a trio of bioinformatics staff members have been hired to maintain a sophisticated database allowing sample searches according to exacting criteria. Lear and a lab supervisor have also come on board to manage the repository’s day-to-day operations.

Likewise updated is the cluster of more than two dozen freezers in which tissue samples are stored, many of which suspend cells in sub-Arctic temperatures as low as minus 196 degrees Celsius. The samples remain in this “vapor phase” until St. Jude technicians pull them out of their frosty confines months or years later to propel scientists’ research efforts.

Although some specimens remain stable for up to 48 hours after collection, others begin deteriorating within 15 minutes. Either way, time is of the essence. 

“The sooner we can cryopreserve the tissue—we snap-freeze it in liquid nitrogen—the better data we’re going to be able to generate when we sequence that sample,” Lear says.

Tissues are preserved in their “native” state, with no specific components—such as genetic material—extracted or analyzed until researchers pinpoint exactly which cell type or fraction they need for a study.

Scientific Stewardship

Obtaining a sample from the Biorepository is a bit like borrowing a library book, in that St. Jude typically requires the sample be returned to allow it to be used again in the future. Researchers at St. Jude and around the globe request these highly sought cells, with a dedicated Tissue Resources Committee meticulously reviewing each application. Samples from St. Jude patients processed by the Biorepository currently support more than 100 clinical trials nationally and internationally.

Many of the studies test drugs that target specific molecules in the samples in hopes of creating or improving treatments.

The prospect of allowing a researcher to deplete any tissue sample is contemplated with extreme care, with sustainability a key philosophy.

“We have specimens going back 40 years, and 40 years from now somebody else should be telling you how we have samples that go back 80 years,” Lear says. “We must continue to care for these samples so their ability to yield clues about particular diseases will be enhanced as time goes on.” 

Carlos Sepulveda sits at a bench on the St. Jude campus.

Like most St. Jude patients, Carlos Sepulveda agreed to have samples of his tumor collected and stored for research. Today, Carlos says he is gratified to know those samples may someday help other patients.

Leap of Faith

Like Carlos, most St. Jude patients who contribute to the Biorepository recognize the gesture is a leap of faith, because they likely won’t ever benefit personally.

“But if I can help make the experience easier mentally or physically—or maybe help alter treatments in the future for someone who’s diagnosed with the same thing—that’s really gratifying,” Carlos says.

For his part, Mullighan can’t forget patients he treated as a new physician who were struggling with leukemia, many of whom died.

“You can get very bogged down in the day-to-day details and mundane aspects of running a lab,” he says. “But we often have very touching stories from patients or relatives who say, ‘We just received a diagnosis of a particular tumor type, and we’d really like you to have that sample in the bank.’”

From Promise, Summer 2017

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