Research Round-up- Clinical & Research News - For and about the Physicians and Researchers of Brigham and Women's HospitalResearch Round-up- Clinical & Research News - For and about the Physicians and Researchers of Brigham and Women's Hospital

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Research Round-up

E. Antonio Chiocca, MD, PhD

Virus Influences Skeletal Muscle Cancer Growth

Previous research studies have suggested that cytomegalovirus (CMV) may play a role in modulating the environment surrounding a tumor, thereby implicating CMV as a key player in tumorigenesis (the formation of tumors).

Recent pre-clinical data from the lab of E. Antonio Chiocca, MD, PhD, BWH chair of Neurosurgery, further supports the hypothesis that CMV contributes to tumor development in the context of Trp53 gene mutation.  

Investigating the effects of cytomegalovirus infection in Trp53 heterozygous mice, the researchers introduced murine cytomegalovirus to the mice at two days of age or four weeks of age. The researchers saw that the mice injected with murine cytomegalovirus at two days of age developed tumors at a high frequency (43 percent) by the time they were nine months old. In contrast, only three percent of mice infected at four weeks, as well as mock-infected mice, developed tumors.

The majority of tumors seen were pleomorphic rhabdomyosarcomas (a type of cancer that develops in skeletal muscles). These tumors contained murine cytomegalovirus DNA, RNA and protein. An examination of clinical cases showed that pleomorphic rhabdomyosarcomas in humans also harbored human cytomegalovirus protein and viral RNA.

"The translational importance of these findings is that treatments to prevent CMV infection in children or antiviral treatments may be utilized to fight against these tumors," said Chiocca.     

The study was published in the Sept. 21, 2012 online issue of Cancer Research.

Cynthia Morton, PhD

Genetic Technology Detects CHARGE Syndrome in Prenatal Sample

A research team led by Cynthia Morton, PhD, BWH director of Cytogenetics, senior study author, conducted a prenatal case study involving a balanced translocation (a genetic abnormality caused by chromosomal rearrangements) between chromosomes 6 and 8 that was not inherited from either parent.

The case study involved performing large-insert sequencing of DNA extracted from amniotic-fluid cells. The sample was taken from a patient in the third trimester of pregnancy who underwent amniocentesis due to severe polyhydramnios after multiple fetal anomalies had been seen on ultrasonography.

The researchers used customized whole-genome "jumping libraries" to identify the precise abnormal areas on the chromosomes and saw a disruption in the CHD7 gene, mutations in which are known to cause CHARGE syndrome (a rare disease that can lead to birth defects of the eyes, ears, heart and other organs). Clinicians diagnosed CHARGE syndrome in the child at birth. The study findings show the potential power of customized whole-genome jumping libraries when used to augment prenatal karyotyping.

The study was published in the Dec. 6, 2012 issue of the New England Journal of Medicine.

Yujiang Geno Shi, PhD

Tet3 Key in Eye and Neural Development

A research team led by Yujiang Geno Shi, PhD, associate biochemist and assistant professor, senior study author, and Yufei Xu, PhD, research fellow, first study author, both of the Division of Endocrinology, BWH Department of Medicine, have defined Tet3 as a key factor in controlling gene expression and embryonic development. Tet3 is a type of enzyme that is involved in regulating the parts of the DNA sequence that instigate gene expression.

In the preclinical study, the researchers found that Tet3 in Xenopus (a type of frog) directly regulates a set of key developmental genes, thereby playing an important role in early eye and neural development. Moreover, further studies showed that specific Tet3 targeting requires a novel DNA binding mode of the Tet3 CXXC domain. Also, the researchers found that the enzymatic activity and CXXC domain are crucial for Tet3's biological function.

"This study has exciting translational value," said Shi. "It offers a foundation for understanding epigenetic dysregulation contributing to eye and brain malformation and diseases, and a basis for designing epigenomic medicines that target and manipulate these dynamic processes in the eye and brain."

The study was published in the Dec. 7, 2012 issue of Cell.