Neuroblastoma may be due to gene interference

Researchers at Sydney's Children's Cancer Institute of Australia (CCIA) have identified a possible mechanism for the formation of tumours from embryonic cells.

Assoc Prof Glenn Marshall said the research, which focused on the role of the MYCN proto-oncogene in the appearance of the early childhood cancer neuroblastoma, suggests there is a "delicate dance" between normal neurodevelopment, and the formation of tumours from embryonic nerve cells, or neuroblasts, in very young children.

"The field has known for many years that a lot of children get this cancer but in many cases it disappears without therapy, so there is a natural defence mechanism against tumour formation," Marshall said. "We're trying to understand the tumour regression process with the hope of developing better treatment and possibly prevention strategies."

Marshall and his colleagues have used a transgenic mouse model for neuroblastoma that closely mimics the human disease, where the MYCN gene is overexpressed in nerve tissue. Surprisingly, they found that in nerve tissues from non-transgenic mice, a short-term proliferation of neuroblasts could be seen in a narrow time window after birth. This pre-cancer spontaneously regressed within the first two weeks. In contrast, in nerve tissues from MYCN transgenic mice, the pre-cancer was larger but underwent a process of regression. However, the regression was delayed and incomplete. They further showed that tumours formed only after secondary changes to the precancerous cells, such as MYCN amplification, occurred in following weeks.

The researchers suggest that neuroblasts are normally deleted before or soon after birth, but in the transgenic mice, the deletion process is delayed and incomplete. Further changes to the neuroblast cells are required for tumour progression. Now they are looking at what factors might cause incomplete deletion of neuroblasts.

"What we've done is try to focus on factors in the normal birth period that are different from child to child that could affect the timing of this process, such as hypoxia or nutritional deficiencies," Marshall said.

He said that hypoxia, for example, had already been shown to protect the precancerous cells from cell death in cell culture.

"We hope to link our findings to precancerous neuroblastoma in children," Marshall said. "This could ultimately lead to preventative treatments -- that's the direction that most excites us."

The research also has implications for the treatment of certain other forms of cancer.

"We hope to be able to generalise to other forms of embryonic cancer," Marshall said.