Instability of short tandem repeats (microsatellites) in human cancers

Abstract

The allele sizes of polymorphic microsatellite repeats in DNA from human cancers were compared to normal DNA from the same patients. In 16 out of 196 paired samples (8%), we found evidence of an extra allele of a different size in the tumour which was not present in the normal DNA. Sequence analysis confirmed that the extra allele originates from the appropriate locus and that the size change is attributable to alteration in the number of repeat units. This form of instability was more common in tri- and tetranucleotide repeats than in dinucleotide repeats. In any single tumour sample only one repeat in the set examined was abnormal, the remainder showing identical patterns in normal and tumour DNA or evidence of allele loss. The pattern of instability in diverse types of cancer differs from that reported in colorectal neoplasms.

Microsatellite instability and loss of heterozygosity in mammary carcinoma and its probable precursors

“…Until such uniformity is achieved, direct comparisons of the results obtained by different research groups is impossible and can lead to wildly different estimates of the rate of MSI in a given tumour type Peltomaki et al, 1993;Patel et al, 1994). If the presence of any MSI is assumed to be indicative of an RER+ phenotype, then the rate of RER+ tumours seen in this study was 10.8%, similar to that reported by Wooster et al (1994).…”

“…Size instability in microsatellite DNA is associated with certain neurological conditions (Willems, 1994) and has been demonstrated more recently in a variety of malignant neoplasms (e.g. Han et al, 1993;Peltomaki et al, 1993;Horii et al, 1994;Wooster et al, 1994). There is in vitro evidence that cells with defective MMR genes carry a high frequency of errors in microsatellite sequences (Liu et al, 1995).…”

“…Both Lothe et al (1993) and Peltomaki et al (1993) saw no instances of MSI in the same series of 84 tumours using the same seven microsatellites. Han et al (1993) recorded 1 of 26 (4%) cases exhibiting MSI with four microsatellites; Wooster et al (1994) saw MSI in 11 of 104 (11%) cases of mammary carcinoma when screening with a panel of 12 markers; Yee et al (1994) used seven microsatellites against 20 breast neoplasms and found instability in 4 of 20 (20%); and Huang et al (1995) demonstrated instability in 9 of 29 (31%) tumours with a series of 10 microsatellite markers. At extreme odds with the other reports, Patel et al (1994) detected instability in 11 of 13 (85%) tumours using nine microsatellites.…”

No evidence of microsatellite instability in bone tumours

“…osteosarcoma, Table I) and none showed MI. However, as a small proportion of soft-tissue sarcomas exhibited a low degree of MI in a previous study (Wooster et al, 1994), it is still possible that microsatellite instability could be detected in a distinct subgroup of bone tumours, at least with a low degree. Furthermore, preliminary results of mice deficient for PMS2 or MSH2 have shown that these animals may be susceptible to developing sarcomas (Baker et al, 1995;de Wind et al, 1995).…”

“…So far mesenchymal tumours have been screened for RER in only one study, in which two of 18 soft-tissue sarcomas exhibited instability with one repeat (Wooster et al, 1994). In a study of loss of heterozygosity (LOH) in chondrosarcomas with markers linked to multiple hereditary exostoses loci no evidence of MI was seen (Raskind et al, 1995).…”