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Stage of development of the tumor eye number 1 in children

18 September 2018 10:11

Researchers at Children's Hospital of Los Angeles were able to determine the exact stage of human retinal development when cells can spiral out of control and form a tumor mass. This finding may open the door for future interventions in the retinoblastoma (RB), retinal tumor that affects children under the age of five years.

The study is a continuation of the work supported by a grant from the National Cancer Institute, and was published online September 13 in the journal PNAS, Proceedings of the National Academy of Sciences.

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The study is the first of its kind, identifying a phase of human retinal development in which specific cells called precursors of the cone, can become cancerous.

"Understanding this stage of development, and what goes wrong, can help us to find ways to intervene and eventually prevent retinoblastoma", - said David Kobrinik, MD, Ph.D., the Vision Center at Children's Hospital Los Angeles.

Although rare, retinoblastoma is the most common malignant tumor of the eye in children and can lead to a devastating loss of vision.

The previous discovery in 2014 that led to this study, the scientists identified CHLA progenitors cone as the retinoblastoma cell of origin. Conical cells in the retina responsible for color vision.

Following the discovery in 2014 in the current study, the team found that at some point in their maturation cone human progenitor cells can enter the cell cycle - a series of events leading to their separation. Then, the cells begin to multiply and form a pre-cancerous tumors that may develop in the fast-growing retinoblastoma-like mass. Precursors ripening cone includes the cell cycle in response to the inactivation of a tumor suppressor gene and loss of RB1 protein functional RB, which regulates cell growth and holds the precursor cells from dividing a cone.

"We suspect that the cone maturation of precursors are connected in such a way that cause them to become cancer cells in response to the loss of the protein RB», - said Kobrinik, Research Institute Investigator CHANA Sabana and associate professor of ophthalmology at Keke School of Medicine at the University of Southern California.

In another case, the key researchers compared the process of development of the human eye with the traditional model of the mouse. Lead author and researcher doktorantny Hardeep Singh, Ph.D., found that the development stage of a particular cell proliferation and the formation of the retinoblastoma occurs in scarce human code precursor protein deficiency, but not in the precursors of the mouse. Animal models have failed to reproduce the genetic, cellular and characteristics of human cells in the retina. This discovery calls into question the accuracy of some models of retinoblastoma animals.

An alternative way to study the state can include induced pluripotent stem cells, Kobrinik said. They can be prepared directly from adult cells, and are another subject of investigation in his laboratory.

Retinoblastoma was among the first tumor who identified the genetic cause. Mutations in tumor suppressor gene RB1 were identified in CHLA and other institutions nearly 30 years ago. Since then, much has been known about how RB1 mutations initiate tumor retinoblastoma.

"Given the current state of genomic analyzes, - said Kobrinik - we look forward to the time when we will be able to test the mutation in the RB1, as well as other genes associated with the disease and to ensure preventive measures."



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