Instability of short tandem repeats (microsatellites) in human cancers

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.

[1]  D. Barnes,et al.  The locus of the polymorphic epithelial mucin (PEM) tumour antigen on chromosome 1q21 shows a high frequency of alteration in primary human breast tumours , 1990, International journal of cancer.

[2]  X. Estivill,et al.  PCR detection of the pKM.19/ScrfI RFLP (D7S23), a marker closely linked to the cystic fibrosis mutation. , 1990, Nucleic acids research.

[3]  H. Hobbs,et al.  Tetranucleotide repeat polymorphism in the LPL gene. , 1990, Nucleic Acids Research.

[4]  J. Weber.  Informativeness of human (dC-dA)n.(dG-dT)n polymorphisms. , 1990, Genomics.

[5]  P. Devilee,et al.  Frequent somatic imbalance of marker alleles for chromosome 1 in human primary breast carcinoma. , 1991, Cancer research.

[6]  D. Nelson,et al.  Triplet repeat mutations in human disease. , 1992, Science.

[7]  R. Richards,et al.  Isolation and characterisation of (AC)n microsatellite genetic markers from human chromosome 16. , 1992, Genomics.

[8]  G. Gyapay,et al.  A second-generation linkage map of the human genome , 1992, Nature.

[9]  M. Stratton,et al.  A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome , 1992, Nature Genetics.

[10]  C. Amemiya,et al.  Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. , 1992, Science.

[11]  David E. Housman,et al.  Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy , 1992, Nature.

[12]  C. Kimpton,et al.  A further tetranucleotide repeat polymorphism in the vWF gene. , 1992, Human molecular genetics.

[13]  Robert I. Richards,et al.  Dynamic mutations: A new class of mutations causing human disease , 1992, Cell.

[14]  J. Weber,et al.  Genetic mapping of a locus predisposing to human colorectal cancer. , 1993, Science.

[15]  H. Willard,et al.  A polymorphic X-linked tetranucleotide repeat locus displaying a high rate of new mutation: implications for mechanisms of mutation at short tandem repeat loci. , 1993, Human molecular genetics.

[16]  K. Kinzler,et al.  Clues to the pathogenesis of familial colorectal cancer. , 1993, Science.

[17]  G. Thomas,et al.  Short direct repeats flanking deletions, and duplicating insertions in p53 gene in human cancers. , 1993, Oncogene.

[18]  J. Mandel,et al.  Linkage disequilibrium between the fragile X mutation and two closely linked CA repeats suggests that fragile X chromosomes are derived from a small number of founder chromosomes. , 1993, American journal of human genetics.

[19]  Manish S. Shah,et al.  A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes , 1993, Cell.

[20]  Darryl Shibata,et al.  Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis , 1993, Nature.

[21]  S N Thibodeau,et al.  Microsatellite instability in cancer of the proximal colon. , 1993, Science.

[22]  J. Mandel,et al.  Origin of the expansion mutation in myotonic dystrophy , 1993, Nature Genetics.

[23]  M. Robertson,et al.  Mutational analysis of patients with adenomatous polyposis: identical inactivating mutations in unrelated individuals. , 1993, American Journal of Human Genetics.

[24]  Shiro Miwa.  Triplet repeats strike again , 1994, Nature Genetics.