Ž . Mutation Research 439 1999 223–232 Identification of individuals at high risk for head and neck carcinogenesis using chromosome aneuploidy detected by fluorescence in situ hybridization Hong Ai a , Jose E. Barrera b , Zhaoxing Pan c , Arlen D. Meyers b , Marileila Varella-Garcia a, ) a Department of Medical Oncology and Colorado Cancer Center, UniÕersity of Colorado Health Sciences Center, Box B188, DenÕer, CO 80262, USA b Department of Otolaryngology, UniÕersity of Colorado Health Sciences Center, DenÕer, CO 80262, USA c Department of PreÕentiÕe Medicine and Colorado Cancer Center, UniÕersity of Colorado Health Sciences Center, DenÕer, CO 80262, USA Received 27 August 1998; revised 7 December 1998; accepted 9 December 1998 Abstract Ž . To visualize the accumulation of chromosome abnormalities in head and neck squamous cell carcinomas HNSCC and Ž . investigate the extension of the abnormal field, we applied the fluorescence in situ hybridization FISH technique to tumor cells and cells collected from a large extension of clinically normal buccal mucosa distant from the tumor in 10 patients. Ž . DNA probes specific for 14 human chromosomes 1, 2, 3, 6, 7, 8, 9, 10, 11, 12, 15, 17, X, and Y were used in dual-target, dual-color FISH assays. Control specimens were collected from oral mucosa of 10 healthy non-smokers, in order to define the tolerance limits for abnormalities, and from 10 healthy smokers. Extensive aneuploidy was detected in most of tumor specimens, more frequently represented by chromosome gains than losses. Interestingly, the clinically normal distant oral regions displayed chromosomal aneuploidies in seven out of the 10 patients tested. These findings support the occurrence of field cancerization in HNSCC. In addition, interphase FISH is demonstrated as an effective technique for detecting chromosome aneuploidy associated with malignancy and a potential tool for non-invasive screening of individuals at high-risk for HNSCC. q 1999 Elsevier Science B.V. All rights reserved. Keywords: Head and neck squamous cell carcinoma; Molecular cytogenetics; Chromosomal imbalance; Tumor risk; Field cancerization 1. Introduction Head and neck tumors represent 2–3% of all human cancers, with an estimated 30,300 new cases wx and 8000 deaths in the USA annually 1 . Approxi- ) Corresponding author. Tel.: q1-303-315-3593; Fax: q1-303- 315-3304; E-mail: marileila.garcia@uchsc.edu mately 90–95% of head and neck tumors are classi- Ž . fied as squamous cell carcinomas HNSCC , and tobacco and alcohol are the most important etiologi- wx cal factors for these tumors 2. A large-scale prospective study has demonstrated that the relative risk of cancer death among ) 35-year old smokers, as compared with non-smokers, was 27.5-fold for oral and pharyngeal cancer and 10.5-fold for laryn- 1383-5718r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. Ž . PII: S1383-5718 98 00199-5