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Hypermutability and mismatch repair deficiency in RER+ tumor cells.

Publication ,  Journal Article
Parsons, R; Li, GM; Longley, MJ; Fang, WH; Papadopoulos, N; Jen, J; de la Chapelle, A; Kinzler, KW; Vogelstein, B; Modrich, P
Published in: Cell
December 17, 1993

A subset of sporadic colorectal tumors and most tumors developing in hereditary nonpolyposis colorectal cancer patients display frequent alterations in microsatellite sequences. Such tumors have been thought to manifest replication errors (RER+), but the basis for the alterations has remained conjectural. We demonstrate that the mutation rate of (CA)n repeats in RER+ tumor cells is at least 100-fold that in RER- tumor cells and show by in vitro assay that increased mutability of RER+ cells is associated with a profound defect in strand-specific mismatch repair. This deficiency was observed with microsatellite heteroduplexes as well as with heteroduplexes containing single base-base mismatches and affected an early step in the repair pathway. Thus, a true mutator phenotype exists in a subset of tumor cells, the responsible defect is likely to cause transitions and transversions in addition to microsatellite alterations, and a biochemical basis for this phenotype has been identified.

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Published In

Cell

DOI

ISSN

0092-8674

Publication Date

December 17, 1993

Volume

75

Issue

6

Start / End Page

1227 / 1236

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Restriction Mapping
  • Repetitive Sequences, Nucleic Acid
  • Polymerase Chain Reaction
  • Oligodeoxyribonucleotides
  • Nucleic Acid Heteroduplexes
  • Mutation
  • Mutagenesis, Insertional
  • Molecular Sequence Data
  • Humans
 

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Parsons, R., Li, G. M., Longley, M. J., Fang, W. H., Papadopoulos, N., Jen, J., … Modrich, P. (1993). Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell, 75(6), 1227–1236. https://doi.org/10.1016/0092-8674(93)90331-j
Parsons, R., G. M. Li, M. J. Longley, W. H. Fang, N. Papadopoulos, J. Jen, A. de la Chapelle, K. W. Kinzler, B. Vogelstein, and P. Modrich. “Hypermutability and mismatch repair deficiency in RER+ tumor cells.Cell 75, no. 6 (December 17, 1993): 1227–36. https://doi.org/10.1016/0092-8674(93)90331-j.
Parsons R, Li GM, Longley MJ, Fang WH, Papadopoulos N, Jen J, et al. Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell. 1993 Dec 17;75(6):1227–36.
Parsons, R., et al. “Hypermutability and mismatch repair deficiency in RER+ tumor cells.Cell, vol. 75, no. 6, Dec. 1993, pp. 1227–36. Pubmed, doi:10.1016/0092-8674(93)90331-j.
Parsons R, Li GM, Longley MJ, Fang WH, Papadopoulos N, Jen J, de la Chapelle A, Kinzler KW, Vogelstein B, Modrich P. Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell. 1993 Dec 17;75(6):1227–1236.
Journal cover image

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

December 17, 1993

Volume

75

Issue

6

Start / End Page

1227 / 1236

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Restriction Mapping
  • Repetitive Sequences, Nucleic Acid
  • Polymerase Chain Reaction
  • Oligodeoxyribonucleotides
  • Nucleic Acid Heteroduplexes
  • Mutation
  • Mutagenesis, Insertional
  • Molecular Sequence Data
  • Humans