Saturday, August 17, 2013

researchers develop new CHLA NextGen sequencing approach to retinoblastoma

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researchers develop new CHLA NextGen sequencing approach to retinoblastoma -

Researchers at the Los Angeles Children's Hospital (CHLA) have developed a unique new generation sequencing test for the gene associated with retinoblastoma. The new approach is both more complete and can be performed in less time than existing tests -. For early detection of genetic cause of cancer, which is essential for optimal treatment results

The test was developed to meet the needs of retinoblastoma program at Vision Center ABSC one of the largest clinical programs in the United States, the care of about 20% of the nation retinoblastoma and see as much as 50 new patients each year. Retinoblastoma - a malignant cancer of childhood that arises from immature retinal cells in one or both eyes - can begin to grow at any time before birth to about seven years. In infants and children, the common signs of this cancer include having a "glow" white or "reflection" in the pupil of one or both eyes, the presence of a white pupil in a color photo, or crossed or misaligned eyes.

Early detection is critical because when untreated, retinoblastoma can cause blindness or death. In the case of the germ line, the disease causing mutation is present in the cells of the organism resulting in tumors in both eyes, as well as in other places in the body. Therefore, early detection and accurate diagnosis are essential to determine the best treatment.

A team of physicians and scientists of the Department of Pathology and Laboratory Medicine Center for Personalized Medicine, in collaboration with clinicians and surgeons Vision Center, developed the ABSC retinoblastoma next generation (RB1 NextGen ) sequencing panel based on the deep DNA sequencing technology, using new technical methods and bioinformatics to sequence the entire gene RB1.

Conventional genetic testing for retinoblastoma usually involves the sequencing of specific hot spots in the gene where it is known to have many changes. When the researchers exposed CHLA to develop their own derivative lab test, they took a very different approach to sequence the entire gene end to end.

"In general, we used sequencing capacity NextGen to the sequence of many genes at a relatively shallow depth of coverage," says Alexander Judkins, MD, FRCP, Head of the Department of Pathology and laboratory medicine. "Our team has taken a very different approach by deciding to look great depth coverage of a single gene, sequencing through the entire gene, which is technically very difficult to do."

With the current approach of retinoblastoma NextGen sequencing, there are gene regions that do examined at all, potentially allowing important information to be missed, added Timothy Triche, MD, Ph.D. , director of the Center for the custom at ABSC medicine. "New data tells us that non-coding DNA is extremely important. And one of the strengths of our approach is to consider the non-coding regions."

By sequencing the entire gene, the researchers were able to see more frequent way of germline mutations of the RB gene. Because germline mutations can transmit this knowledge can better inform the correct treatment approach for patients when these mutations are identified.

"We used to think that if a child had a tumor in one eye and not in the other eye, it is the result of a somatic mutation. And because somatic carriers do not pass on mutated genes, tumor removal was believed stopped the cancer, "says Tom Lee, MD, director of the Vision Center at CHLA" But now we know there is a percentage -. the order of 10 to 15% those children who had an apparent somatic mutation - which are actually carrying a germline mutation, putting them at risk of developing these tumors during adolescence or adulthood. "

Lee said that the ability to determine the existence of RB1 mutations in the germ-line early major consequences - not only for prognosis of a new patient with retinoblastoma, but for siblings could also be at risk and eventually own children to a patient if a germline mutation is detected in a retinoblastoma survivor could be passed on to future generations.

deal with hundreds of children with retinoblastoma inheritance, ABSC now also has the ability to offer this unique and comprehensive screening test for survivors of the disease or their family members, and for patients with other cancer centers. "We believe the siblings and children of carriers of the germ line should be tested immediately after birth because by detecting mutations early gene can save the vision of a patient," said Lee.

Approximately two thirds of patients with retinoblastoma ABSC have unilateral RB case, or cancer in one eye. While only 15% of cases will test positive for a germline mutation, physicians must treat all patients as if cancer could be bilaterial or present in both eyes, a condition often associated with having a germline mutation. "Historically, genetic tests can take up to three or four months, which is a very long time when the health of a child is at stake," said Jonathan Kim, MD, director of the retinoblastoma program at CHLA. "Making our tests more quickly and on site has the potential to significantly improve treatment outcomes for all our patients."

"This test allows our researchers to look at the gene RB1 more global," Judkins said. "The collection of new genomic data RB1 hopefully allow basic researchers to translate this knowledge into hardware biologically significant, leading to earlier detection and new treatments for diseases of both primary and recurrent. "


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