Investigators from St. Jude Children’s Research Hospital will present their research at the annual meeting of the American Association for Cancer Research (AACR). The five-day international meeting begins April 1 in Washington, D.C.
© AACR/Todd Buchanan 2016
Select Oral Abstracts
Featured Study
DATE: April 3
TIME: 3:20 p.m.
LOCATION: Room 204, Level 2, Washington Convention Center
TITLE: Germline mutations in cancer predisposition genes and risk for subsequent neoplasms among long-term survivors of childhood cancer in the St. Jude Lifetime Cohort
ABSTRACT: 3001
Whole genome sequencing of more than 3,000 long-term St. Jude childhood cancer survivors found that 12 percent carried mutations in one of 156 genes that are associated with an increased risk of cancer for survivors or their children. The St. Jude study is apparently the first to use whole genome sequencing to explore the contribution of genetics to lifetime cancer risk in survivors. The findings prompted the researchers to recommend expanding genetic screening and counseling to include more long-term survivors. “While there is extensive scientific literature on the late effects of cancer therapy, including the risk that survivors will develop subsequent malignancies, until now little was known about the contribution of genetic factors,” said Jinghui Zhang, PhD, Computational Biology chair. She and Leslie Robison, PhD, Epidemiology and Cancer Control chair, were the study’s co-senior authors. The study involved survivors enrolled in the St. Jude Lifetime Cohort study (St. Jude LIFE). Among survivors whose initial cancer treatment did not include radiation therapy, those who carried pathogenic or likely pathogenic mutations were five times more likely to develop another malignancy than those who did not. Among survivors who were previously treated with radiotherapy, those who carried pathogenic or likely pathogenic mutations were at a 12-fold increased risk for subsequent breast cancer, a four-fold elevated risk of thyroid cancer and a 12-fold elevated risk of sarcoma compared to survivors without such mutations. Zhaoming Wang, PhD, of Computational Biology, and Carmen Wilson, PhD, of Epidemiology and Cancer Control, were co-first authors. Wang presented the findings.
DATE: April 2
TIME: 3:35 p.m.
LOCATION: Room 144, Level 1, Washington Convention Center
TITLE: Non-myogenic origin of embryonal rhabdomyosarcoma
ABSTRACT: 1036
Rhabdomyosarcoma, the most common soft tissue cancer in children, was long thought to originate exclusively in early skeletal muscle cells. Research led by Mark Hatley, MD, PhD, of St. Jude Oncology, has shown that certain embryonal rhabdomyosarcoma tumors arise from early endothelial cells instead. About 60 percent of children with rhabdomyosarcoma have the embryonal subtype. “Despite aggressive therapy, clinical outcomes for rhabdomyosarcoma have not improved for three decades,” Hatley said. “That fact underscores the need to uncover the molecular basis of this disease to identify new vulnerabilities to attack this cancer.” The study focused on embryonal rhabdomyosarcoma caused by mutations in the Sonic Hedgehog signaling pathway and used a mouse model developed in Hatley’s laboratory. Cell lineage tracing analysis helped researchers identify early endothelial cells as the cell of origin for the tumor subtype. Catherine Drummond, PhD, a St. Jude postdoctoral fellow, will present the findings.
DATE: April 3
TIME: 4:05 p.m.
LOCATION: Room 204, Level 2, Washington Convention Center
TITLE: Comparison of somatic alterations in the genome and transcriptome of 1,705 pediatric leukemia and solid tumors: a report from the Children’s Oncology Group (COG) - NCI TARGET Project
ABSTRACT: 3004
Comprehensive genetic sequencing of more than 1,000 pediatric cancer patients showed that whole genome sequencing is necessary to capture all of the genetic alterations driving childhood cancer, which are often different from the mutations responsible for cancer in adults. St. Jude researchers led the analysis of data from the National Cancer Institute's TARGET Initiative. "Just 44 percent of the pediatric cancer driver mutations in this study matched those identified in adults," said senior author Jinghui Zhang, PhD, St. Jude Computational Biology chair. She said the findings underscored the importance of sequencing the whole genome, not just the protein-coding regions — or exome — to identify the mutations driving cancer in children. "Just 48 percent of the driver mutations in this study were point mutations, which means that whole genome sequencing was required to identify the full spectrum of alterations driving the cancers," Zhang said. Researchers also used single-cell sequencing to study the interplay of genetic and epigenetic factors in cancer. The study involved whole genome, whole exome and RNA sequencing of tumor and normal tissue from 1,705 pediatric patients with different types of leukemia and solid tumors. The patients were treated through the Children’s Oncology Group, a clinical trials network that includes medical centers in the U.S. and Canada. The TARGET Initiative is focused on identifying and understanding the molecular changes that drive childhood cancers. Study data are publicly available through the NCI’s Genome Data Commons (gdc.cancer.gov) and can also be explored via the St. Jude ProteinPaint data portal (pecan.stjude.org). Xiaotu Ma, PhD, Computational Biology, will present the findings.
DATE: April 3
TIME: 4:20 p.m.
LOCATION: Room 204, Level 2, Washington Convention Center
TITLE: Whole-genome sequencing identified novel non-coding mutations causal of oncogene activation in T-cell acute lymphoblastic leukemia
ABSTRACT: 3005
St. Jude researchers working with collaborators in China and Singapore have reported evidence that mutations in non-coding regions of the human genome contribute to leukemia in children and may offer promising targets for treatment in the future. Once dismissed as “junk,” non-coding regions of the genome are sections of DNA that do not encode instructions for assembling proteins. Whole genome and whole transcriptome sequencing of 31 pediatric Asian patients with T-cell acute lymphoblastic leukemia found that about 10 percent had the same alteration in a non-coding region of DNA. “We went looking for genomic abnormalities of ALL specifically in Asians because of their unique genetic background and also the paucity of studies focusing on this population despite the fact that half of children with leukemia worldwide are in Asia. We were not disappointed,” said senior author Jun J. Yang, PhD, Pharmaceutical Sciences. “This integrated analysis showed that this newly identified mutation dramatically increased expression of LMO1, an oncogene known to drive T-ALL.” The finding was confirmed in an additional 26 patients from Asia. Work in cell lines found evidence leukemic cells require LMO1 for survival, which suggests it might be a viable therapeutic target. Maoxiang Qian, PhD, a postdoctoral fellow in Yang’s laboratory, will present the research.
DATE: April 3
TIME: 4:35 p.m.
LOCATION: Room 204, Level 2, Washington Convention Center
TITLE: Oncogenic activity of H3.3 K27M in a spontaneous DIPG mouse model
ABSTRACT: 3006
Despite advances in treatment of pediatric cancer, the brain tumor diffuse intrinsic pontine glioma (DIPG) still has a dismal prognosis. Suzanne Baker, PhD, Developmental Neurobiology, and her colleagues have developed the first mouse model of this high-grade glioma. They used the model to determine how a point mutation in a family of DNA packaging proteins called histone H3 drives formation and the continued growth of DIPG and other high-grade gliomas that develop in and around the thalamus. The mutation H3K27M occurs in nearly 80 percent of DIPGs and more than half of the other high-grade gliomas, a finding that was reported previously by Baker and others. “DIPG is a tumor that is only found in brains undergoing development,” Baker said. “Understanding how this mutation works raises the possibility of developing strategies to counteract its impact.” Jon Larson, PhD, a postdoctoral fellow in Baker’s laboratory, will present the findings.
St. Jude Experts Participating in AACR
In addition to the investigators noted above, St. Jude experts on site include:
Visit Us at Booth #3232
Representatives from the St. Jude Office of Academic Programs will be available to answer questions in the Exhibit Hall at Booth #3232.
Join Us at the AACR Career Fair
DATE: April 1
TIME: 9 a.m. – 3 p.m.
LOCATION: East Hall, Salons B and C, Washington Convention Center
TITLE: AACR Cancer & Biomedical Research Career Fair