Bulletin Spring‧Summer Autumn‧Winter 1999

The Missing Pieces on Chromosomes 3 and 9 Prime Suspects in Nasopharyngeal Cancer NPC Common among Hong Kong Chinese Nasopharyngeal cancer, more properly called nasopharyngeal carcinoma (NPC), is most commonly found in Southern Chinese. Many people in Hong Kong know of friends and relatives who have been afflicted by this dread disease. If diagnosis is made early and treatment is given appropriately, a substantial proportion of patients can be cured, and the relapse-free survival rate can be as high as over 80 per cent w i t h i n 10 years. The Faculty of Medicine at The Chinese University of Hong Kong is a leading institution of research on the causes and treatment of various forms of cancer. A n d the Cancer Centre in its teaching hospital, the Prince of Wales Hospital, is so far the only centre of excellence established by the Hospital Authority to tackle problems related to cancer. Recent wo rk by Dr. Dolly P. Huang and her colleagues at the University's Department of Anatomical and Cellular Pathology has led to the i d e n t i f i c a t i on of t wo p r i me suspects — chromosomes 3 and 9 — i n the genetic development of NPC. This significant advance is likely to lead to improved understanding of the disease, and ultimately to better techniques of diagnosis and treatment. This project w o n competitive funding of $160,000 from the Research Grants Council in 1992 and an additional $566,000 for further support for two years in 1993. How the Cancer Develops It has long been recognized that NPC may have a variety of interwoven causes. There is strong evidence linking this cancer to three well defined factors: (a) a close association w i th the ubiquitous Epstein-Barr virus, (b) certain traditional Southern Chinese diets containing chemical carcinogens, coupled w i t h insufficient intake of fresh fruits and vegetables and, (c) an inherited genetic predisposition to the disease in certain patients. The relative importance of these factors in causing NPC, and their mutual interaction, are not well understood. However, it is thought that these factors, in isolation or in combination, cause multiple gene alterations in tumour suppressor genes and the p r o t o - oncogenes. These genetic alterations lead to a multi-step loss of normal gene functions, and d i s r upt the harmonious checks and balances which regulate cell growth and development. The accumulation of such genetic alterations in the nasopharyngeal mucosal cells w i l l eventually lead to the development of nasopharyngeal cancer. Chromosomes 3 and 9 Implicated With the rapid advancement of molecular biology i n the last few decades, investigation of such genetic events has become increasingly important in cancer research. Dr. Huang's research team has demonstrated that in NPC cancer cells, there is a consistent and nonrandom loss of segments on the short arms of chromosome 3 and chromosome 9 at specific locations (3p14 and 9p21). This has been demonstrated by cytogenetic analysis and by 'detailed deletion mapping' on the short arms of both chromosomes w i th 21 overlapping genetic markers (Microsatellite Polymorphisms Analysis) as illustrated in Figs. 1 and 2. Findings like these, and the consistency w i t h wh i ch such genetic defects occur i n patients suggest that NPC- associated suppressor genes reside on the short arms of bo th chromosomes at the identified regions. The defects and the loss of functions of these genes facilitate the development of the cancer. Research 11