Matt Lear is the Technical Director of the St. Jude Biorepository.

Biorepository is ‘Library’ of the Pediatric Cancer Genome Project

The St. Jude Biorepository collects and stores biomedical samples, allowing scientists to explore the origins of pediatric cancer and develop new diagnostic tests and therapies. 

By Keith Crabtree, PhD; Photos by Seth Dixon and Ann-Margaret Hedges

Sarahbeth Howes was diagnosed with embryonal rhabdomyosarcoma, a soft tissue tumor, when she was 15 years old.

“I was a sophomore in high school; I was on the varsity soccer team; I was in honors classes,” she says. “I had a lot going for me.”

Sarabeth Howes

When asked to donate tissue to the St. Jude Children’s Research Hospital Biorepository to be used for research, she quickly agreed.

“If I could help someone else,” says Howes, now a third-year medical student, “I was all for it, and so was my family.”

Recently, Howes hit the 10-year survivorship mark — “a pretty big deal in the survivorship world,” she says. Coincidentally, the Pediatric Cancer Genome Project (PCGP) also marked its 10th anniversary. This project has revolutionized our understanding of the genetic factors that underpin rare pediatric cancers. More than 800 patients donated tissue samples for use in the PCGP; 66% of those samples came from the St. Jude Biorepository.

The Library

The Biorepository, also known as the tissue bank, isn’t a financial institution. You won’t find a drive-through teller or an ATM. You won’t find a bank vault, even though stringent security measures are in place. The Biorepository is more like a library that collects and stores biological samples instead of books. To protect privacy, specimen samples are coded to reveal important clinical data without patient names or other identifiers.

Researchers approved by the hospital’s Tissue Resource Distribution Committee and the Institutional Review Board can “check out” samples to explore basic genomic questions.

Technical Director Matt Lear says the Biorepository’s first sample was collected in 1976. A reorganization of the collection in the early 2000s marked the beginning of the modern era of the tissue bank. In 2015, its name was changed from the Tissues Resources Core Facility to the St. Jude Biorepository.

microscope

The Biorepository collects the little bits of material that remain after procedures such as blood draws and surgeries. Staff members place that tissue in the racks of nearly 30 tall freezers cooled with liquid nitrogen to temperatures as low as -196 degrees Celsius.

The facility stores more than 500,000 samples from children with solid tumors, brain tumors, leukemia and non-malignant blood disorders, such as sickle cell disease and bone marrow failure syndromes. The specimens come from patients in active treatment and, increasingly, long-term survivors taking part in the hospital’s long-term follow-up study, St. Jude LIFE.

PCGP scientists sequenced about 3,400 samples for use in the PCGP and its offshoot studies. The facility also supports about 200 clinical trials worldwide.

Charles Mullighan, MBBS, MD, the Biorepository’s medical director, was a member of the PCGP steering committee.

“I extracted the first 20 samples that were sequenced,” he says. Today, sample extraction, processing, storage, distribution and other day-to-day tasks are handled by a cadre of lab technicians.

Biorepository lab personnel

Quiet Achievers

The Biorepository was small — a side room connected to a pathology lab — when the PCGP launched in 2010. Since then, the facility has had a three-fold increase in lab technicians and the addition of three bioinformatics experts, which required moving to a larger, dedicated space.

Mullighan often commends his staff for their hard work and ingenuity, dubbing them “quiet achievers.” For example, when the Biorepository needed new sample-tracking software, the team tried a disappointing off-the-shelf product.

 “Out of frustration with the new software, they said, ‘We can do this so much better,” Mullighan said. “And within a week, they mocked up their own version and showed that it could work.”

Charles Mullighan

“We want to make our inventories as future-proof as we can. We never know what’s coming down the line.”

Charles Mullighan, MBBS, MD

Voluntary Donations

At one point during her treatment, Howes lost her ability to walk.

“For my 16th birthday, I got a walker instead of a car,” Howes recalls. For an athlete who used exercise to cope with stress, it was devastating. But the hardships of her cancer journey didn’t sway her decision to donate tissue to the Biorepository. She says she found meaning in the idea of paying it forward, of contributing toward future research efforts.

More than 95% of St. Jude families agree to donate tissue samples. The conversations about that donation, however, are sometimes delicate. Suzanne Baker, PhD, who directs the Division of Brain Tumor Research, has spent years researching an incurable brain tumor called diffuse intrinsic pontine glioma (DIPG). Located deep in the brain, these tumors were not typically biopsied, which limited research.

Oncologist and clinical collaborator Alberto Broniscer, MD, formerly of St. Jude, suggested approaching families to discuss planned autopsy donations. At first, Baker was unsure how parents would respond to a request for tumor samples to be taken after a child’s death.

“Overall, families shared that donation was important to them, that it gave some meaning to what they had gone through,” says Baker, who, along with Jinghui Zhang, PhD, Computational Biology chair, identified a DIPG mutation that had never been found before.

“This specific mutation in histone H3 is found in 80% of these brain tumors,” Baker says. “It’s potentially a new target for therapy.”

Mulligan and Baker credit the children and their families who have donated samples to fill the Biorepository.

“We have focused so much effort on these rare pediatric cancers. In many cases, it involved many years of treating patients with these diseases and collecting clinical samples so that there was material available for research,” Baker says.

matt lear

Future Proof

Biorepository staff try to preserve samples in their native state in the hope that tissues will be fit for as many potential research uses as possible.

One way to safeguard the specimens is through the Biorepository’s Noah’s Ark program, an insurance policy of sorts. To prepare for an unlikely disaster, a portion of the facility’s samples are stored at an offsite location, an accredited lab in the Northeast. Biorepository staff can monitor and retrieve the samples at any time.

The Biorepository is expanding its physical footprint, with space in the new Shared Resource Center and more space to come when the Advanced Research Center opens in spring of 2021. These facilities will advance the Biorepository’s transition from manual, time-consuming processes to automated, robotic ones. Sample extraction, processing and storage will be more efficient and of higher quality.

“We want to make our inventories as future-proof as we can,” Mullighan says. “We never know what’s coming down the line.”

*Photos for this article were taken pre-COVID-19.

From Promise, Special Edition 2020

 
 

St. Jude Biorepository

  • Contains more than 500,000 tissue samples donated over the past 44 years by St. Jude patients
  • About 5,000 specimens donated each month
  • Includes nearly 30 freezers cooled with liquid nitrogen
  • Cells suspended in temperatures as low as -196 degrees Celsius
  • One of the first 5 banks nationwide to be accredited by the College of American Pathologists
  • Supports about 200 clinical trials worldwide
  • About 3,400 samples from the bank sequenced as part of the Pediatric Cancer Genome Project and its offshoot studies
 
 

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