Wednesday, June 13, 2012

How a Quirky Fruit Fly Gene Could Help Researchers Develop New Cancer Drugs

MAYWOOD, Ill. -- Loyola researchers are taking advantage of a quirk in the evolution of fruit fly genes to help develop new weapons against cancer.

A newly discovered fruit fly gene is a simplified counterpart of two complex human genes that play important roles in the development of cancer and some birth defects. As this fruit fly gene evolved, it split in two. This split has made it easier to study, and the resulting insights could prove useful in developing new cancer drugs.

"Evolution has given us a gift," said Andrew K. Dingwall, PhD, senior author of a paper that describes how his team identified and analyzed the split gene. Their findings are published in the June issue of the prestigious journal Development.  Based on the importance of the findings, the paper was recently selected as an "Editor's Choice" in Science Signaling, published by the American Association for the Advancement of Science (AAAS).

When normal cells develop, they differentiate into particular types, such as bone cells or muscle cells, and reproduce in an orderly manner. The process is governed by genes and hormones that work in concert. Two of these genes are known as MLL2 and MLL3. Cancer cells, by contrast, undergo uncontrolled division and reproduction.

Since 2010, a growing number of cancers have been linked to mutations in the MLL2 and MLL3 genes. These cancers include non-Hodgkin’s lymphoma, colorectal cancer, kidney cancer, bladder cancer and a brain tumor called medulloblastoma. There also is evidence that MLL2 and MLL3 mutations are involved in breast and prostate cancers.

The MLL2 and MLL3 genes are similar to one another. Each has more than 15,000 building blocks called base pairs -- more than 10 times the number found in a typical gene. Because these genes are so large and complex, they are difficult to study.

In the fruit fly, the counterpart gene to MLL2 and MLL3 split into two genes named TRR and CMI. Each carried information critical for normal gene regulation, and they wound up on different chromosomes. The parsing of the MLL2/MLL3 genetic information into smaller genes in the fruit fly made study of the gene functions much easier; it allowed the researchers unprecedented opportunities to explore the role the human genes play in the development of cancers.

"This fruit fly gene gives us unique insight into the massive human MLL2 and MLL3 genes that are almost impossible to study because they are so large," Dingwall said.

Dingwall's team studied the function of the fruit fly gene by inducing various mutations and then observing the effects on the flies. This will lead to better understanding of what goes wrong when mutations in MLL2 and MLL3 genes trigger the uncontrolled reproduction of cancer cells in humans. This in turn could help researchers develop drugs that would redirect cancer cells to differentiate into normal cells, Dingwall said.

The study was funded through a grant from the National Science Foundation, with additional support from the National Institutes of Health.

Dr. Dingwall is an associate professor in the Oncology Institute and Department of Pathology at Loyola University Chicago Stritch School of Medicine. Co-authors are Claudia Zraly, PhD (joint first author and senior co-author); Chhavi Chauhan (joint first author); Megan Parilla; and Manuel Diaz, MD.

About Loyola University Health System

Loyola University Health System (LUHS) is a member of Trinity Health. Based in the western suburbs of Chicago, LUHS is a quaternary care system that includes Loyola University Medical Center (LUMC), located on a 61-acre campus in Maywood, Gottlieb Memorial Hospital (GMH), on a 36-acre campus in Melrose Park, and convenient locations offering primary and specialty care services throughout Cook, Will and DuPage counties. At the heart of LUMC is a 547-licensed-bed hospital that houses the Center for Heart & Vascular Medicine, the Cardinal Bernardin Cancer Center, a Level 1 trauma center, a burn center, a children's hospital, Loyola Outpatient Center, and Loyola Oral Health Center. The campus also is home to Loyola University Chicago Stritch School of Medicine, Loyola University Chicago Marcella Niehoff School of Nursing and the Loyola Center for Fitness. The GMH campus includes a 254-licensed-bed community hospital, a Professional Office Building with 150 private practice clinics, an adult day care program, the Gottlieb Center for Fitness, the Loyola Center for Metabolic Surgery and Bariatric Care and the Loyola Cancer Care & Research at the Marjorie G. Weinberg Cancer Center at Melrose Park.

Trinity Health is one of the largest multi-institutional Catholic health care delivery systems in the nation. It serves people and communities in 22 states from coast to coast with 93 hospitals, and 120 continuing care locations — including home care, hospice, PACE and senior living facilities — that provide nearly 2.5 million visits annually.