Consistent molecular genetic variation in human gastrointestinal carcinomas

Abstract

Investigations of chromosomal variation in human cancer have shown that malignancy is not necessarily associated with karyotypic aberration (for example, 30% of acute lymphoblastic leukaemias show no obvious changes¹) and that the vast majority of alterations that do occur are of a random nature^2,3. Only a few consistent chromosomal aberrations have been cytologically associated with human cancer, most notable of which are the Philadelphia translocation of chronic myelocytic leukaemia⁴, a deletion in chromosome 11 in Wilm's tumour⁵ and a deletion in chromosome 13 in ∼2% of retinoblastomas⁶. It is known that highly repetitive DNA is diminished after serial passage of human diploid fibroblasts in culture⁷ and it is not unreasonable to suggest that loss or redistribution of genetic material could occur generally in neoplastic tissues, as proliferating tumour cells might be subjected to similar selective pressures. Here we show that, in human gastrointestinal carcinomas, the overall degeneration of DNA sequence organization as suggested by almost all cytogenetic evidence is not random and that unstable regions of the genome can be clearly distinguished from others that remain highly conserved even in advanced states of neoplasia. Quantitative assessment of such data could form the basis of an assay for early malignant transformation in gut and other human tissues.