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Mononucleotide precedes dinucleotide repeat instability during colorectal tumour development in Lynch syndrome patients.
J Pathol. 2009 Sep; 219(1):96-102.JP

Abstract

A progressive accumulation of genetic alterations underlies the adenoma-carcinoma sequence of colorectal cancer. This accumulation of mutations is driven by genetic instability, of which there are different types. Microsatellite instability (MSI) is the predominant type present in the tumours of Lynch syndrome patients and in a subset of sporadic tumours. It is generally accepted that MSI can be found in the early stages of tumour progression, such as adenomas; however, the frequencies reported vary widely among studies. Moreover, data on the qualitative differences between adenomas and carcinomas, or between tumours of hereditary and sporadic origin, are scarce. We compared MSI in samples of colorectal adenoma and colorectal carcinoma in order to identify possible differences along the adenoma-carcinoma sequence. We compared germline mismatch repair (MMR) gene mutation carriers and non-carriers, to address possible differences of instability patterns between Lynch syndrome patients and patients with sporadic tumours. We found a comparable relative frequency of mono- and dinucleotide instability in sporadic colorectal adenomas and carcinomas, dinucleotide instability being observed most frequently in these sporadic tumours. In MMR gene truncating mutation carriers, the profile was different: colorectal adenomas showed predominantly mononucleotide instability and in colorectal carcinomas, also more mononucleotide than dinucleotide instability was detected. We conclude that MSI profiles differ between sporadic and Lynch syndrome tumours, and that mononucleotide marker instability precedes dinucleotide marker instability during colorectal tumour development in Lynch syndrome patients. As mononucleotide MSI proves to be highly sensitive for detecting mutation carriers, we propose the use of mononucleotide markers for the identification of possible Lynch syndrome patients.

Authors+Show Affiliations

Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19521971

Citation

Ferreira, Ana M., et al. "Mononucleotide Precedes Dinucleotide Repeat Instability During Colorectal Tumour Development in Lynch Syndrome Patients." The Journal of Pathology, vol. 219, no. 1, 2009, pp. 96-102.
Ferreira AM, Westers H, Sousa S, et al. Mononucleotide precedes dinucleotide repeat instability during colorectal tumour development in Lynch syndrome patients. J Pathol. 2009;219(1):96-102.
Ferreira, A. M., Westers, H., Sousa, S., Wu, Y., Niessen, R. C., Olderode-Berends, M., van der Sluis, T., Reuvekamp, P. T., Seruca, R., Kleibeuker, J. H., Hollema, H., Sijmons, R. H., & Hofstra, R. M. (2009). Mononucleotide precedes dinucleotide repeat instability during colorectal tumour development in Lynch syndrome patients. The Journal of Pathology, 219(1), 96-102. https://doi.org/10.1002/path.2573
Ferreira AM, et al. Mononucleotide Precedes Dinucleotide Repeat Instability During Colorectal Tumour Development in Lynch Syndrome Patients. J Pathol. 2009;219(1):96-102. PubMed PMID: 19521971.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mononucleotide precedes dinucleotide repeat instability during colorectal tumour development in Lynch syndrome patients. AU - Ferreira,Ana M, AU - Westers,Helga, AU - Sousa,Sónia, AU - Wu,Ying, AU - Niessen,Renée C, AU - Olderode-Berends,Maran, AU - van der Sluis,Tineke, AU - Reuvekamp,Peter T W, AU - Seruca,Raquel, AU - Kleibeuker,Jan H, AU - Hollema,Harry, AU - Sijmons,Rolf H, AU - Hofstra,Robert M W, PY - 2009/6/13/entrez PY - 2009/6/13/pubmed PY - 2009/10/10/medline SP - 96 EP - 102 JF - The Journal of pathology JO - J. Pathol. VL - 219 IS - 1 N2 - A progressive accumulation of genetic alterations underlies the adenoma-carcinoma sequence of colorectal cancer. This accumulation of mutations is driven by genetic instability, of which there are different types. Microsatellite instability (MSI) is the predominant type present in the tumours of Lynch syndrome patients and in a subset of sporadic tumours. It is generally accepted that MSI can be found in the early stages of tumour progression, such as adenomas; however, the frequencies reported vary widely among studies. Moreover, data on the qualitative differences between adenomas and carcinomas, or between tumours of hereditary and sporadic origin, are scarce. We compared MSI in samples of colorectal adenoma and colorectal carcinoma in order to identify possible differences along the adenoma-carcinoma sequence. We compared germline mismatch repair (MMR) gene mutation carriers and non-carriers, to address possible differences of instability patterns between Lynch syndrome patients and patients with sporadic tumours. We found a comparable relative frequency of mono- and dinucleotide instability in sporadic colorectal adenomas and carcinomas, dinucleotide instability being observed most frequently in these sporadic tumours. In MMR gene truncating mutation carriers, the profile was different: colorectal adenomas showed predominantly mononucleotide instability and in colorectal carcinomas, also more mononucleotide than dinucleotide instability was detected. We conclude that MSI profiles differ between sporadic and Lynch syndrome tumours, and that mononucleotide marker instability precedes dinucleotide marker instability during colorectal tumour development in Lynch syndrome patients. As mononucleotide MSI proves to be highly sensitive for detecting mutation carriers, we propose the use of mononucleotide markers for the identification of possible Lynch syndrome patients. SN - 1096-9896 UR - https://www.unboundmedicine.com/medline/citation/19521971/Mononucleotide_precedes_dinucleotide_repeat_instability_during_colorectal_tumour_development_in_Lynch_syndrome_patients_ L2 - https://doi.org/10.1002/path.2573 DB - PRIME DP - Unbound Medicine ER -