Stepwise Deletions of PolyA Sequences in Mismatch Repair-deficient Colorectal Cancers

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2001 May 5

PMID 11337385

Citations 18

Authors

C Blake

J L Tsao

A Wu

D Shibata

Affiliations

Soon will be listed here.

Abstract

PolyA simple repeat sequence deletions are common in tumors with microsatellite instability (MSI+). Such deletions occur one base at a time in DNA mismatch repair (MMR)-deficient yeast suggesting larger deletions in human MSI+ tumors represent multiple sequential stepwise losses. Sum total deletions in four polyA repeats were variable (between -17 to -45 bp) in 20 sporadic MSI+ colorectal cancers. Progressive but less extensive total deletions (maximum of -12 bp) occurred in similar polyA sequences in MMR-deficient mice (mlh1-/-) up to 478 days old. PolyA repeat lengths were relatively stable but already shortened in the MMR-deficient cell line HCT116. A transgene with 26 A's transfected into HCT116 shortened an average of 3.8 bases pairs after 469 days in culture, less than average deletions of BAT25 (-5.3) or BAT26 (-9.0) in MSI+ cancers. These findings further suggest that extensive polyA deletions common in MSI+ tumors likely reflect multiple stepwise smaller deletions that accumulate more than hundreds of divisions after loss of MMR.

Citing Articles

A Subset of Microsatellite Unstable Cancer Genomes Prone to Short Insertions over Deletions Is Associated with Elevated Anticancer Immunity.

Kim S, Han D, Lee S, Moon Y, Kang S, Kim T Genes (Basel). 2024; 15(6).

PMID: 38927706 PMC: 11202581. DOI: 10.3390/genes15060770.

The clinical significance of PD-L1 in advanced gastric cancer is dependent on mutations and ATM expression.

Buglioni S, Melucci E, Sperati F, Pallocca M, Terrenato I, De Nicola F Oncoimmunology. 2018; 7(8):e1457602.

PMID: 30221053 PMC: 6136851. DOI: 10.1080/2162402X.2018.1457602.

Deep sequencing and pathway-focused analysis revealed multigene oncodriver signatures predicting survival outcomes in advanced colorectal cancer.

De Nicola F, Goeman F, Pallocca M, Sperati F, Pizzuti L, Melucci E Oncogenesis. 2018; 7(7):55.

PMID: 30032163 PMC: 6054833. DOI: 10.1038/s41389-018-0066-2.

Rapid generation of hypomorphic mutations.

Arthur L, Chung J, Jankirama P, Keefer K, Kolotilin I, Pavlovic-Djuranovic S Nat Commun. 2017; 8:14112.

PMID: 28106166 PMC: 5263891. DOI: 10.1038/ncomms14112.

Morphological characterization of colorectal cancers in The Cancer Genome Atlas reveals distinct morphology-molecular associations: clinical and biological implications.

Shia J, Schultz N, Kuk D, Vakiani E, Middha S, Segal N Mod Pathol. 2016; 30(4):599-609.

PMID: 27982025 PMC: 5380525. DOI: 10.1038/modpathol.2016.198.

References

Kane M, Loda M, Gaida G, Lipman J, Mishra R, Goldman H . Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res. 1997; 57(5):808-11. View

Kinzler K, Vogelstein B . Lessons from hereditary colorectal cancer. Cell. 1996; 87(2):159-70. DOI: 10.1016/s0092-8674(00)81333-1. View

Tran H, Keen J, Kricker M, Resnick M, Gordenin D . Hypermutability of homonucleotide runs in mismatch repair and DNA polymerase proofreading yeast mutants. Mol Cell Biol. 1997; 17(5):2859-65. PMC: 232138. DOI: 10.1128/MCB.17.5.2859. View

Tsao J, Davis S, Baker S, Liskay R, Shibata D . Intestinal stem cell division and genetic diversity. A computer and experimental analysis. Am J Pathol. 1997; 151(2):573-9. PMC: 1857988. View

Zhou X, Hoang J, Cottu P, Thomas G, Hamelin R . Allelic profiles of mononucleotide repeat microsatellites in control individuals and in colorectal tumors with and without replication errors. Oncogene. 1998; 15(14):1713-8. DOI: 10.1038/sj.onc.1201337. View

Goldstein D, Pollock D . Launching microsatellites: a review of mutation processes and methods of phylogenetic interference. J Hered. 1998; 88(5):335-42. DOI: 10.1093/oxfordjournals.jhered.a023114. View

Prolla T, Baker S, Harris A, Tsao J, Yao X, Bronner C . Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair. Nat Genet. 1998; 18(3):276-9. DOI: 10.1038/ng0398-276. View

Boland C, Thibodeau S, Hamilton S, Sidransky D, Eshleman J, Burt R . A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998; 58(22):5248-57. View

Lettieri T, Marra G, Aquilina G, Bignami M, Crompton N, Palombo F . Effect of hMSH6 cDNA expression on the phenotype of mismatch repair-deficient colon cancer cell line HCT15. Carcinogenesis. 1999; 20(3):373-82. DOI: 10.1093/carcin/20.3.373. View

10.

Yao X, Buermeyer A, Narayanan L, Tran D, Baker S, Prolla T . Different mutator phenotypes in Mlh1- versus Pms2-deficient mice. Proc Natl Acad Sci U S A. 1999; 96(12):6850-5. PMC: 22005. DOI: 10.1073/pnas.96.12.6850. View

11.

Schwartz Jr S, Yamamoto H, Navarro M, Maestro M, Reventos J, Perucho M . Frameshift mutations at mononucleotide repeats in caspase-5 and other target genes in endometrial and gastrointestinal cancer of the microsatellite mutator phenotype. Cancer Res. 1999; 59(12):2995-3002. View

12.

Tsao J, Yatabe Y, Salovaara R, Jarvinen H, Mecklin J, Aaltonen L . Genetic reconstruction of individual colorectal tumor histories. Proc Natl Acad Sci U S A. 2000; 97(3):1236-41. PMC: 15581. DOI: 10.1073/pnas.97.3.1236. View

13.

Percesepe A, Pedroni M, Sala E, Menigatti M, Borghi F, Losi L . Genomic instability and target gene mutations in colon cancers with different degrees of allelic shifts. Genes Chromosomes Cancer. 2000; 27(4):424-9. View

14.

Streisinger G, Okada Y, Emrich J, Newton J, Tsugita A, Terzaghi E . Frameshift mutations and the genetic code. This paper is dedicated to Professor Theodosius Dobzhansky on the occasion of his 66th birthday. Cold Spring Harb Symp Quant Biol. 1966; 31:77-84. DOI: 10.1101/sqb.1966.031.01.014. View

15.

Loeb L . Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 1991; 51(12):3075-9. View

16.

Ionov Y, Peinado M, Malkhosyan S, Shibata D, Perucho M . Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993; 363(6429):558-61. DOI: 10.1038/363558a0. View

17.

Strand M, Prolla T, Liskay R, Petes T . Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature. 1993; 365(6443):274-6. DOI: 10.1038/365274a0. View

18.

Shibata D, Peinado M, Ionov Y, Malkhosyan S, Perucho M . Genomic instability in repeated sequences is an early somatic event in colorectal tumorigenesis that persists after transformation. Nat Genet. 1994; 6(3):273-81. DOI: 10.1038/ng0394-273. View

19.

Parsons R, Li G, Longley M, Modrich P, Liu B, Berk T . Mismatch repair deficiency in phenotypically normal human cells. Science. 1995; 268(5211):738-40. DOI: 10.1126/science.7632227. View

20.

Branch P, Bicknell D, Rowan A, Bodmer W, Karran P . Immune surveillance in colorectal carcinoma. Nat Genet. 1995; 9(3):231-2. DOI: 10.1038/ng0395-231. View