Loss of heterozygosity on chromosome arm 16q in breast cancer: clinical, molecular and statistical approaches
© Current Science Ltd 2000
Published: 12 March 2000
Loss of heterozygosity (LOH) on the long arm of chromosome 16 is one of the most frequent genetic events in breast cancer, occurring in at least 50% of the breast cancer cases. It is one of the earliest genetic events, occurring already in the pre-invasive stage, in ductal carcinoma in situ. Our study on flow-sorted tumour populations shows that chromosome 16q loss occurs in the DNA diploid sub-population of tumour cells, before aneuploidization, which is also indicative of a role in early tumorigenesis.
A detailed LOH analysis using 30 highly polymorphic markers and careful revision of the histology of a series of 200 primary invasive breast tumours could not demonstrate any significant correlation between LOH on 16q and histopathological markers. On the contrary there was a markedly higher number of cases with 16q LOH in a series of well differentiated pre-invasive breast cancers when compared with poorly differentiated pre-invasive tumours. This suggests a difference in time of occurrence of 16q LOH in these two morphological distinguishable groups, ie early LOH in well differentiated tumours and late (upon invasion) in the poorly differentiated subset.
Since mapping of the smallest region of deletion involved in LOH has not yet resulted in identification of the tumour suppressor genes which are the target of 16q LOH, we have applied a novel statistical approach for the analysis of our data using an improved version of the model described previously by Newton et al (Statist Med 1998, 17:1425). The program has been improved by introducing the possibility for the existence of more than one tumour suppressor locus and by increasing its speed by some orders of magnitude. Analysis of 16q LOH data in breast cancer with this program provides evidence for the presence of two different tumour suppressor loci on chromosome arm 16q.