St. Jude redefines diagnostic ‘gold standard’
Recent St. Jude findings suggest that whole-genome sequencing should be used for all children with cancer.
This process involves determining the exact order, or sequence, of the 3 billion chemical bases that make up human DNA.
The method isn’t widely used because of cost and time constraints.
Most pathology departments that issue sequencing results look at only a panel of several hundred genes. That approach can miss many important mutations. More advanced institutions may look only at the whole exome and whole transcriptome. The exome encodes instructions for assembling proteins. The transcriptome identifies the genes that are expressed. Together, those two methods can find 78 percent of cancer-causing mutations.
But when St. Jude researchers combined whole-genome sequencing with those two approaches, 99 percent of mutations were identified.
Whole-genome testing is now offered to every new St. Jude cancer patient.
Scientists shared these findings in the journal Nature Communications. Data from the study are also available in St. Jude Cloud’s PeCan portal.
How Hippo pathway may affect solid tumor growth
Like detectives tracking a serial killer, St. Jude scientists have identified a novel mechanism that may explain how two oncogenes promote the growth and spread of solid tumors.
The research focused on two proteins called YAP and TAZ, which activate gene expression and drive cell growth. YAP and TAZ are controlled by the Hippo signaling pathway.
But how YAP/TAZ contributes to tumor growth and spread had been unclear.
One possible answer? Hypertranscription.
“Rather than activating a few genes involved in cell proliferation, activation of YAP/TAZ caused a global increase in gene transcription activity, or hypertranscription,” said Xinwei Cao, PhD, of St. Jude Developmental Neurobiology,
Researchers are using results of this study to explore how YAP/TAZ activation may influence development of other solid tumors. The findings appeared in the journal Developmental Cell.
Immune housecleaners morph into cancer fighters
Ever let dishes pile up while you deal with a crisis? Scientists at St. Jude have a new strategy to reprogram certain immune cells inside tumors so that they focus on killing cancer cells rather than tidying up after tumor cells die.
The plan involves a process the scavenger immune cells use to digest the dead and dying tumor cells they pick up for disposal. Researchers showed that disabling the process in the immune cells transformed them from housecleaners to cancer fighters.
“Understanding this fundamental process holds a key to future treatments,” Green said. “We have already embarked on approaches to applying our findings.”
The research appeared in the journal Cell.
Small risks may have big impact on breast cancer odds
Female survivors of childhood cancer have among the highest breast cancer rates of any group. Using data from the St. Jude LIFE study, scientists found common genetic variations that can help identify those who have a higher risk for breast cancer.
The research focused on 170 common genetic variations. Individually, each confers a small breast-cancer risk. But together, they can double the breast-cancer risk for women who survived childhood cancer. The threat is greatest for those under 45 years of age.
“When combined with screening for rare mutations in breast cancer predisposition genes, these findings are expected to help identify high-risk pediatric cancer survivors who currently go unrecognized,” said Zhaoming Wang, PhD, of St. Jude Epidemiology and Cancer Control and Computational Biology.
The findings were published in the journal Clinical Cancer Research.
What can salad dressing tell us about cancer? Think oil and vinegar.
The process explaining why oil and vinegar separate in salad dressing may also play a role in prostate cancer and other solid tumors.
St. Jude scientists found that mutations in the tumor suppressor gene SPOP contribute to cancer by disrupting a process called liquid-liquid phase separation. This process is the reason oil and vinegar separate in salad dressing.
The SPOP protein binds unneeded or unwanted proteins so they can be tagged for destruction. SPOP mutations were known to disrupt binding and lead to a buildup of cancer-promoting proteins in sensitive cells.
“This study shows for the first time that mutations in the tumor-suppressor SPOP disrupt phase separation and that tumor-suppressor function can be influenced by phase separation at all,” said Tanja Mittag, PhD, of St. Jude Structural Biology.
The findings appeared in the journal Molecular Cell.
Map unveils secrets of brain development
St. Jude researchers have created a massive database of the changes in gene activity of individual cells in the cerebellum during development and immediately after birth. The cerebellum, a key brain control center, contains more than half of all nerve cells in the central nervous system.
The St. Jude project created a high-resolution map. It allows scientists to view the genomic changes cells undergo as the cerebellum develops.
The research provides a basis for understanding the origins of brain disorders caused by errors in development. The database will enable scientists to trace the cellular origins of certain childhood brain tumors.
Researchers worldwide can interact with the data through the St. Jude Cell Seek interface.
A report on this project appeared in the journal Current Biology.
New resource will advance leukemia research
St. Jude has created the world’s largest collection of acute leukemia models from children and adults.
PROPEL (Public Resource of Patient-derived and Expanded Leukemias), aims to advance global research in acute leukemia. The project shares unique, patient-derived xenograft samples with researchers worldwide.
PROPEL samples are offered free of charge to researchers. Recipients have no obligation to collaborate, which is unique in the research community. The xenografts, and the matching primary patient samples, include detailed genome sequencing data. They also often contain drug-response data.
“Despite therapeutic advances and improved outcomes, we must make progress to cure leukemia with more effective, less-toxic therapies tailored to each type of leukemia,” said Charles Mullighan, MD, MBBS, of St. Jude Pathology. “We hope to accelerate discovery and cures for leukemia and improve long-term outcomes for survivors.”