DELETION MAPPING OF CHROMOSOME-3 IN LUNG-TUMORS

The ability to stain chromosomes to obtain a reproducible, chromosome specific, banding pattern, a technique developed in the early 1970s [26], allowed the complex karyotypes of tumour cells to be studied in such a way that many distinct chromosome abnormalities were shown to be tumour specific [19]. In 1982 Whang-Peng described the karyotypes of 20 small cell lung cancer (SCLC) samples, mainly cell lines, all of which had deletions in the short arm of chromosome 3 [24]. Such a high degree of concordance between a disease and a cytogenetic abnormality is unusual, and was difficult to evaluate at that time because another study of SCLC karyotypes identified deletions in only 3/14 samples [25]. However, the importance of genetic damage to chromosome 3 in this disease became‘irrefutable when the technique of restriction fragment length polymorphism (RFLP) analysis was applied to large numbers of tumour samples, and showed unequivocally that alleles on chromosome 3 were lost in virually all SCLC tumours [2,16,17]. This suggested that even those cell lines without visible deletions would be expected to have lost alleles on chromosome 3. One possibility was that these cell lines carried a deletion too small to be distinguished by light microscopy, and might, therefore, have been useful reagents in the search for important genes within the deleted region. We applied RFLP analysis to DNA isolated from five such cell lines using probes for nineteen polymorphisms on chromosome 3, and found that these cell lines had lost alleles by whole homologue loss, with reduplication of the remaining homologue, rather than microdeletion [21]. These cell lines were therefore not useful to search for small deletions, but did indicate how the discrepancy between cytogenetic and RFLP analysis might be explained; namely that although all SCLC tumours lose alleles from chromosome 3, a