P R E S S   R E L E A S E

      Dr Lam Ching-wan of The Chinese University of Hong Kong discovers that mutations of a proto-oncogene will cause two common types of cancer: basal-cell carcinoma (BCC) and medulloblastomas.  His research finding provides the important foundation for developing medical therapy of these cancers. 

      BCC is a common skin tumor in humans with over a million cases a year worldwide, showing a continuing increase in incidence. The tumor grows slowly and rarely metastasizes or causes death. Nevertheless, BCC can cause considerable disease through local invasion and tissue destruction. Treatment of BCC is usually by surgical removal, but recurrence is common because the full tumor is difficult to remove, and repeated surgeries are often necessary. BCCs usually arise in elderly light-skinned people as sporadic tumors, but are also a major feature of the nevoid basal cell carcinoma syndrome, an unusual genetic disorder characterized primarily by cancer susceptibility and some embryonic abnormalities. 

      Recently, insight into the molecular origins of BCCs came from the identification of mutations in the PATCHED gene (PTCH) in patients with nevoid basal cell carcinoma syndrome. The protein encoded by the PTCH gene normally inhibits another protein, Smoothened.  When PTCH has been inactivated by mutation in nevoid basal cell carcinoma syndrome, Smoothened is turned on continuously, providing a continuous signal to the cell to grow. 

      The research by Dr Lam and his collaborators from University of California, San Francisco and Genetech, Inc. which was published in Nature, a world's leading scientific journal, identifies an activating mutation in the Smoothened (SMO) gene in sporadic BCCs. The findings provide direct evidence that mutated SMO can function as a cancer-causing oncogene in BCC.  Further study also revealed this mutation in medulloblastomas, the most common paediatric brain tumor, the cause of which the medical profession still does not know. 

      "Finding this mutation in two distinct tissues suggests that this signalling pathway may also be involved in causing other cancers as well.  And more in-depth research into this gene may make us know more about cancer," said Dr Lam. 

      PTCH was originally discovered in fruitflies, commonly used in laboratory for genetic studies. The PTCH gene in humans is the homologous form to that in flies.  Genetic studies in fruitflies show that PTCH is part of a molecular signalling system, or pathway, which is important in determining the patterns of embryonic cell and tissue development.  The fact that this signalling pathway exists in humans indicates that it has been evolutionarily conserved and must be playing a critical role in development. 

      Dr Lam's study also provides useful information for the development of medical therapy of these cancers.  A simple way to control such cancers is to turn off the Smoothened gene which, as identified by the scientist, when turned on causes cancer.   In contrast, turning off the PTCH gene also causes cancer. Pharmacological manipulation of these genes might have wide-ranging implications for a rational medical therapy of cancer, and especially basal cell carcinoma. 

      Dr Lam Ching-wan is an assistant professor at the Department of Chemical Pathology, The Chinese University of Hong Kong.