In 2010, St. Jude Children’s Research Hospital and Washington University School of Medicine launched a $65 million, three-year project to sequence the complete normal and cancer genomes of 600 pediatric cancer patients.

The goal was to define the genomic landscape of pediatric cancer, including some of the least understood and most challenging cancers.

At the time, large-scale sequencing projects focused primarily on adult cancers. St. Jude researchers sought to fill that void with the largest investment and most comprehensive effort to identify and understand the genetic origins of cancer.

The St. Jude—Washington University Pediatric Cancer Genome Project became the world’s most ambitious effort to discover the origins of childhood cancer and seek new cures.

In all, researchers sequenced the complete and normal genomes of about 800 pediatric cancer patients. The project included whole exome and whole transcriptome sequencing of an additional 1,200 patients, which included 23 different cancers.

Groundbreaking discoveries

In the past decade, scientists pinpointed mutations not previously linked to cancer, identified subtype-specific mutations in the brain tumor medulloblastoma, defined novel cancer subtypes, highlighted the developmental context of cancer and revealed the role epigenetics plays in some pediatric cancers.

Published in the New England Journal of Medicine in 2015, we found a surprisingly high percentage of pediatric cancer patients carry germline mutations in known cancer predisposition genes. Almost 1 in 10 of the 1,120 children and adolescents in the study carried such a mutation.

In addition, more than 35 research papers have appeared in peer-reviewed journals, including some of the most prestigious, such as the New England Journal of MedicineNature and Nature Genetics.

The findings have been incorporated into clinical trials underway at St. Jude, through the Children’s Oncology Group and internationally, that aim to improve cure rates and long-term outcomes for children with acute lymphoblastic leukemia, medulloblastoma, diffuse intrinsic pontine glioma and other childhood cancers.

Current clinical trials designed to improve treatment and outcomes for children with cancer reflect the findings and insights gained from the project. The trials include SJMB12, an international clinical trial for young people with medulloblastoma, TOTAL XVII for children with acute lymphoblastic leukemia and others.

In 2014, the Pediatric Cancer Genome Project laid the foundation for the creation of the St. Jude Cancer Predisposition Clinic. The clinic helps children and families who may have inherited genetic mutations that leave them at higher-than-normal risk of cancer. More than 2,500 patients have been evaluated by clinic staff and close to 500 families with an underlying cancer predisposition have been identified.

In 2018, St. Jude launched an online data-sharing and collaboration platform that provides researchers access to the world's largest public repository of pediatric cancer genomics data. Developed as a partnership among St. Jude, DNAnexus and Microsoft, St. Jude Cloud provides accelerated data mining, analysis and visualization capabilities in a secure cloud-based environment.

Researchers have developed more than a half dozen data analysis and visualization tools. The tools include CREST, CISERO, CONSERTING, ProteinPaint, PeCanPie and others. These tools have reduced the data error rate, recognized mutations driving cancer and made it easier for researchers worldwide to interrogate data—either their own or data generated by the Pediatric Cancer Genome Project.

The Childhood Solid Tumor Network and PROPEL support preclinical research into pediatric solid tumors and blood cancers such as leukemia. The human tumor samples provide the global research community with a free resource to advance understanding and treatment of pediatric cancer.

By comparing the complete genomes from cancerous and normal cells for about 800 patients, we have successfully pinpointed the genetic factors behind some of the toughest pediatric cancers. We are now using multiple approaches to analyze cancer genomes even more deeply. We are also developing a state-of-the-art clinical genomics program to better diagnose and treat children with cancer.

Raw sequence data for all published results, as well as data analysis and visualization tools, are freely available. Explore them today to advance your research and help us find cures.

Selected highlights

Selected Highlights


Whole-genome sequencing should be included in diagnostic testing

We showed that incorporating whole-genome sequencing into clinical genomic testing helps identify more high-risk mutations in cancer patients. The results redefined the gold standard for diagnostic testing of children with cancer in the precision medicine era.

Original article: Nature Communications, September 2018
News release: Researchers find a ‘critical need’ for whole genome sequencing of young cancer patients

Comprehensive genomic analysis yields rhabdomyosarcoma drug candidate

We identified a promising precision medicine that is now in clinical trials in combination chemotherapy for rhabdomyosarcoma, a common childhood solid tumor. The candidate drug was identified in research that included what is likely the most comprehensive integrated analysis of the developmental origins of rhabdomyosarcoma.

Original article: Cancer Cell, August 2018
News release: Integrated analysis finds vulnerabilities to target in a high-risk pediatric tumor

Mining the pediatric cancer genome for treatment clues

We collaborated with scientists at the German Cancer Research Center, Heidelberg, to provide the most comprehensive analysis yet of the genomic landscape of multiple childhood cancers. About half the tumors had mutations that might make them vulnerable to precision medicines that are available or in clinical trials.

Original article: Nature, February 2018
News release: Genomic analysis underscores need for precision therapies that target pediatric cancer, February 2018

Sharing a powerful resource with the global scientific community

To fuel new discoveries and treatments, we offer researchers access to the world’s largest collection of pediatric solid tumor samples and related drug sensitivity data at no charge. The resource, known as the Childhood Solid Tumor Network, is the result of a collaboration between St. Jude and the Howard Hughes Medical Institute and has already sparked research advances.

Original article: Nature, August 2017
News release: St. Jude unveils powerful resource to advance treatment of pediatric solid tumors

Scanning for immunotherapy opportunities in childhood cancers

We conducted the first comprehensive analysis of neoepitopes—potential targets of immunotherapies—in pediatric cancers. Going forward, researchers can use this library of potential targets to develop and test cancer therapies that use the immune system to fight cancer cells. 

Original article: Genome Medicine, August 2017

Map offers scientists a new path to understanding retinoblastoma and degenerative retinal diseases

We created a genomic map of the intricate changes in the "epigenetic" organization of the nucleus to determine how retinal cells transition from immature cells to mature retinal neurons. The researchers also mapped the epigenome of retinoblastoma cells as they turn cancerous.

Original article: Neuron, May 2017
News release: St. Jude maps genome organization to link retinal development and retinoblastoma

Selected Highlights


Protein pair altered in a childhood leukemia

In collaboration with the Children’s Oncology Group, we found genetic changes underpinning a subtype of acute lymphoblastic leukemia (ALL), the most common childhood cancer. The changes affect the interplay between DUX4 and ERG, two proteins that control crucial genes in human blood cells. The results have led to new diagnostic approaches in leukemia.

Original article: Nature Genetics, October 2016
News release: Genetic hallmarks of acute lymphoblastic leukemia subtype uncovered

Mapping the genome of an acute myeloid leukemia

We completed a detailed map of the genomic changes found in a childhood leukemia called core-binding factor acute myeloid leukemia (CBF-AML). The research identified new genetic changes that may work with known mutations to cause disease. It also highlighted genes that may influence relapse.

Original article: Nature Genetics, October 2016
News release: Researchers reveal genomic landscape of core-binding factor acute myeloid leukemia

Critical mutations identified in rare low-grade brain tumors

We discovered key mutations that drive the growth of rare brain cancers called low-grade gliomas and glioneuronal tumors. Potential therapies targeting some of these mutations are already being tested in clinical trials. The discovery may also help improve diagnosis of these tumors.

Original article: Acta Neuropathologica, January 2016
News release: Sequencing reveals genetic alterations for uncommon brain tumors in children

An elegant app for mining cancer genome data

We developed a Web-based application, ProteinPaint, that makes it easy for scientists to visualize and explore cancer genome data. The tool includes information on nearly 27,500 mutations from more than 1,000 pediatric patients with 21 cancer subtypes. ProteinPaint is freely available to the research community.

Original article: Nature Genetics, December 2015
News release: St. Jude researchers develop powerful interactive tool to mine data from cancer genome

Defining the genetic causes of childhood cancer

In a large-scale, landmark study, we found that nearly one out of 10 childhood cancer patients was born with an increased genetic risk for cancer. We also discovered unexpected links between adult cancer genes and childhood disease.

Original article: New England Journal of Medicine, November 2015
News release: New study suggests more than 8 percent of children with cancer have genetic predisposition  

A dramatically improved tool for detecting alterations in tumors

We developed CONSERTING, a new computer tool for identifying mutations called copy number alterations (CNAs). The tool finds CNAs, which are involved in many cancers, with much higher accuracy and sensitivity than other techniques. CONSERTING is freely available to the research community.

Original article: Nature Methods, June 2015
News release: Scientists dramatically improve method for finding common genetic alterations in tumors

Large genetic alteration may hold key to treating aggressive infant leukemia

We found that a highly aggressive form of leukemia in infants has surprisingly few mutations beyond a known chromosomal rearrangement that affects the MLL gene. The findings suggest that targeting the alteration is likely the key to improved survival. The study is the most comprehensive analysis yet of this rare subtype of pediatric acute lymphoblastic leukemia (ALL).

Original article: Nature Genetics, April 2015
News release: Chromosomal rearrangement is the key to progress against aggressive infant leukemia

A first genome-wide look at childhood adrenocortical tumors

We pinpointed key mutations involved in pediatric adrenocortical tumors, which had never before been analyzed on a genomic scale. Genomic alterations affecting the genes TP53 and IGF2 were found to occur early in tumor growth, pointing to a key role in triggering tumor development. The results may help clinicians identify children with the most aggressive forms of the disease and lead to improved treatments.

Original article: Nature Communications, March 2015
News release: Researchers map "genomic landscape" of childhood adrenocortical tumors for the first time

Sun damage linked to childhood skin cancer

We found the first genetic evidence that sun damage contributes to melanoma in children and teens, underscoring the importance of starting sun protection early. We also found that melanoma in some teen patients has many of the same genetic alterations as conventional melanoma in adults and is likely to respond to the same therapy.

Original article: Journal of Investigational Dermatology, March 2015
News release: Sun damage causes genetic changes that predispose children and adolescents to melanoma

Understanding how leukemia cells survive chemotherapy

In collaboration with the Children’s Oncology Group and the TARGET initiative, we discovered key details of how acute lymphoblastic leukemia (ALL) cells mutate to survive chemotherapy. The findings may improve early detection of mutations that drive relapse of the disease.

Original article: Nature Communications, March 2015
News release: Scientists trace genomic evolution of high-risk leukemia

Selected Highlights


Mutations in Ewing sarcoma linked to poor survival

We found that alterations in two genes, STAG2 and TP53, are associated with reduced survival for patients with Ewing sarcoma, a tumor of the bone and soft tissue. The findings are an important step toward improved diagnosis and treatment strategies.

Original article: Cancer Discovery, November 2014
News release: Gene sequencing projects link two mutations to Ewing sarcoma subtype with poor prognosis

Genetic clues lay foundation for new leukemia clinical trial

We pinpointed genes linked to a leukemia subtype known as Ph-like ALL and discovered that the subtype grows more common with age. We also learned that many patients might benefit from drugs already used to treat adult leukemias. Combined with earlier work, the findings lay the foundation for an upcoming clinical trial.

Original article: The New England Journal of Medicine, September 2014
News release: Genomic analysis reveals that high-risk leukemia subtype becomes more common with age

Mutations tied to brain tumors in young patients

We found new genetic mutations that occur most often in younger patients with a subgroup of brain tumors known as high-grade gliomas. The findings provide urgently needed drug development leads for this devastating cancer.

Original article: Nature Genetics, April 2014
News release: Gene sequencing project discovers mutations tied to deadly brain tumors in young children

Key gene identified for bone cancer

We discovered that mutations in the tumor suppressor gene TP53 are likely to play a key role early in the development of osteosarcomas, the most common childhood bone cancer. The study also helps explain why this tumor is often resistant to standard-dose radiation therapy.

Original article: Cell Reports, April 2014
News release: Tumor suppressor gene TP53 mutated in 90 percent of most common childhood bone tumor

Catching a brain tumor culprit

We identified the most common genetic alteration ever reported in the brain tumor ependymoma, as well as evidence that the alteration drives tumor development. The findings provide a new foundation for diagnosis and treatment of ependymoma and should aid efforts to understand and intervene against other cancers, including adult tumors.

Original article: Nature, February 2014
News release: Gene sequencing project discovers common driver of a childhood brain tumor

Potential new uses for existing drugs

We found the first evidence that rhabdomyosarcoma, a cancer of muscles and other soft tissues, might be sensitive to drugs that enhance a process called oxidative stress. The drugs killed tumor cells growing in the laboratory. Some medications that harness this cellular process are already on the market.

Original article: Cancer Cell, December 2013
News release: Gene sequencing project finds family of drugs with promise for treating childhood tumor

Two mutations to blame for majority of diffuse low-grade gliomas

We discovered that mistakes in two genes are responsible for more than 50 percent of diffuse low-grade gliomas, a subtype of the most common childhood tumor of the brain and spine. We also found evidence the tumors might be vulnerable to drugs already in development.

Original article: Nature Genetics, April 2013
News release: Gene sequencing project finds new mutations to blame for a majority of brain tumor subtype

Decoding ALS and other degenerative disorders

We discovered new gene mutations linked to a family of diseases that includes amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. The findings could spur new advances in treating some of the most common degenerative disorders of the muscle, brain and bone.

Original article: Nature, March 2013
News release: Two new genes linked to amyotrophic lateral sclerosis (ALS) and related disorders

Uncovering the genetic basis of high-risk leukemias

We discovered new genetic defects in childhood leukemia subtypes that exhibit dramatic chromosome loss and poor cure rates. We also identified a possible treatment strategy using drugs already used to treat other cancers.

Original article: Nature Genetics, January 2013
News release: Genetic basis of high-risk childhood cancer points to possible new drug treatment strategy

Selected Highlights


New methods for mining “junk” DNA

We developed a method to mine the repetitive DNA sequences at the ends of chromosomes for clues about the mistakes fueling cancer and insight into one mutation’s contribution.

Original article: Genome Biology, December 2012
News release: Gene sequencing project mines data once considered 'junk' for clues about cancer

New leads on a rare leukemia subtype

We discovered a genetic alteration responsible for almost 30 percent of cases of AMKL, an uncommon subtype of childhood leukemia. The finding paves the way for desperately needed treatment advances.

Original article: Cancer Cell, November 2012
News release: Gene sequencing project identifies abnormal gene that launches rare childhood leukemia

Promising drug targets for common childhood brain cancers

We uncovered new genetic factors behind medulloblastoma, the most common malignant childhood brain tumor. Some of the genes are already the focus of ongoing drug development efforts.

Original article: Nature, July 2012
News release: Gene sequencing project identifies potential drug targets in common childhood brain tumor

Clues about clinical trends seen in nervous system tumor

We identified a gene mutation that may help explain why outcomes for children with advanced neuroblastoma, a tumor of the nervous system, vary dramatically depending on the child's age at diagnosis.

Original article: Journal of the American Medical Association, March 2012
News release: Genome sequencing initiative links altered gene to age-related neuroblastoma risk

New treatment possibility for eye tumors

We found new clues about why eye tumors known as retinoblastomas tend to develop rapidly. Based on the findings, we identified a promising treatment lead for this fast-moving cancer.

Original article: Nature, January 2012
News release: Gene identified as a new target for treatment of aggressive childhood eye tumor

Surprising genetic links for a high-risk leukemia

We found unexpected genetic alterations in a deadly type of childhood leukemia called early T-cell precursor (ETP)-ALL that could change diagnosis and treatment for children with this disease.

Original article: Nature, January 2012
News release: Cancer sequencing project identifies potential approaches to combat aggressive leukemia

Tracing the genetic underpinnings of brain tumors

We found that a startling 78 percent of the brainstem tumors known as diffuse intrinsic pontine glioma (DIPG) carried changes in two genes not previously linked to cancer.

Original article: Nature Genetics, January 2012
News release: Cancer sequencing initiative discovers mutations tied to aggressive childhood brain tumors

Speeding discovery by improving analysis methods

We developed a new computational model, CREST, to evaluate mutations and control for potential errors. This algorithm outperforms prior tools so well it is being adopted globally.

Original article: Nature Methods, June 2011