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A nude mouse with tumours (left); locations of the two China cancers (right)

The trail to discovering genes involved in two forms of cancer prevalent in Hong Kong and China is being blazed at The Hong Kong University of Science and Technology (HKUST). Researchers are using techniques in molecular genetics to search for the genes that normally suppress tumour activity.
“We have already found at least two in chromosome 3 that are definitely involved and another 17 that are suspect because of their mapping positions,” said Principal Investigator Professor Maria Li Lung.
The research method used involves transferring normal human chromosomes, which comprise many genes, into human cancer cells. The subsequent hybrid cells are tested to see whether they induce cancer in a mouse. Cancer development is halted if tumour suppression genes from the normal transferred chromosome complement defective genes in the original cancer cells.
Prof Lung said: “The suppression genes are very important; not only should they be present and active in preventing tumours, they control cell cycles, telling the cell whether to keep dividing or to die. If the tumour suppression genes are knocked out or lost, then the cell goes awry.”
The two cancer forms of particular interest to Prof Lung are nasopharyngeal carcinoma (NPC), sometimes referred to as the Guangdong Cancer, and oesophageal carcinoma (ESC) which has the highest incidence in the world in China’s Hebei province. The cancers also have a high mortality rate in Hong Kong. NPC attacks the nasal-pharynx area. ESC, which has a lower incidence rate but is more deadly than NPC, occurs in the oesophagus.
As with other cancers, both are caused by defective genes which may have been inherited or damaged by factors such as a diet high in carcinogens, pollution, or even medication. Prof Lung’s molecular research is the first of its kind for NPC and, of the body’s 23 pairs of chromosomes, she and her researchers have homed in on four: chromosomes 3, 9, 11 and 14.
Several candidate genes have been implicated for chromosomes 3, 11 and 14. For chromosome 9, a known tumour suppressor gene, p16, is involved. Another important find has been that chromosome 17 is not involved in NPC although within it resides one of the most common tumour suppressing genes.
The research method is to inject established cancer cells prepared from an NPC patient under the skin of a “nude” mouse which has no thymus and is therefore immune deficient. Without intervention, tumours begin to grow within a couple of weeks. If a normal human chromosome with intact tumour suppression genes is fused with the cancer cell, tumour development is halted.
Conversely, if the tumour suppression genes are defective, tumours will continue to grow.

Principal Investigator
Prof Maria Li Lung: bomaria@ust.hk