Abstract
Recently, we and others reported instability in the (C)8 repeat in exon 5 of MSH6 as a preferential target for somatic mutations in tumours from MSH6 germline mutation carriers. Here, we report that in 45% of tumours from MLH1, MSH2 and MSH6 germline mutation carriers no sequence change in the (C)8 repeat of MSH6 was found upon DNA sequencing analysis of PCR products with a shift in electrophoresis mobility. Using ‘standard’ PCR primers a high frequency of instability (50–86%) of the (C)8 repeat was found, but using a modified PCR reverse primer, accomplishing modulation of non-templated addition of adenine during in vitro PCR amplification by the Taq polymerase, a markedly lower frequency of instability was found in tumours from MLH1, MSH2 and MSH6 mutation carriers (6, 13 and 40%, respectively). Furthermore, a significant difference of the frequency of instability of the (C)8 repeat in tumours from MSH6 mutation carriers was found compared to MLH1, MSH2 mutation carriers. These results might have important implications for the detection of instability of other short mononucleotide repeats, e.g. TGFβRII, BAX, IGFRII, PTEN, BRCA2.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Akiyama Y, Sato H, Yamada H, Nagasaki H, Tsuchiya A, Abe R, Yuasa Y . 1997 Cancer Res. 57: 3920–3923
Akiyama Y, Iwanaga R, Ishikawa T, Sakamoto K, Nishi N, Nihei Z, Iwama T, Saitoh K, Yuasa Y . 1996 Cancer 78: 2478–2484
Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Fodde R, Vasen H, Bigas-Rodriquez M, Srivastava SA . 1998 Cancer Res. 58: 5248–5257
Brownstein MJ, Carpten JD, Smith JR . 1996 Biotechniques 6: 1004–1010
De Leeuw WJF, Diersen JW, Vasen HFA, Wijnen JTh, Kenter GG, Meijers-Heijboer H, Brocker-Vriends A, Stormorken A, Moller P, Menko F, Cornelisse CJ, Morreau H . 2000 J. Pathol. 192: 328–335
Fishel R . 1999 Nature Med. 5: 1239–1240
Guanti G, Resta N, Simone C, Cariola F, Demma I, Florente P, Gentile M . 2000 Hum. Mol. Genet. 9: 283–287
Kolodner RD, Tytell JD, Schmeits JL, Kane MF, Gupta RD, Weger J, Wahlberg S, Fox EA, Peel D, Ziogas A, Garber JE, Syngal S, Anton-Culver H, Li FP . 1999 Cancer Res. 59: 5068–5074
Koul A, Nilbert M, Borg A . 1999 Genes, Chromos. Cancer 24: 207–212
Knudson AG . 1971 Proc. Natl. Acad. Sci. 68: 820–823
Magnuson VL, Ally DS, Nyland SJ, Karanjawala ZE, Rayman JB, Knapp JI, Lowe AL, Ghosh S, Collins FS . 1996 Biotechniques 4: 700–709
Malkhosyan S, Rampino N, Yamamoto H, Perucho M . 1996 Nature 382: 499–500
Markowitz S, Wang J, Myeroff L, Parsons R, Sun L, Lutterbaugh J, Fan R, Zborowska E, Kinzler K, Vogelstein B, Brattain M, Willson J . 1995 Science 268: 1336–1338
Miyaki M, Konishi M, Tanaka K, Kikichi-Yanoshita R, Muraoka M, Yasuno M, Igari T, Koike M, Chiba M, Mori T . 1997 Nature Genet. 17: 271–272
Parsons R, Myerhoff LL, Liu B, Willson JKV, Markowitz SD, Kinzler KW, Vogelstein B . 1995 Cancer Res. 55: 5548–5550
Peltomaki P, Vasen HFA, the International Collaborative Group on Hereditary Colorectal Cancer . 1997 Gastroenterology 113: 1146–1158
Planck M, Wenngren E, Borg A, Olsson H, Nilbert M . 2000 Genes Chromosomes Cancer 29: 33–39
Rampino N, Yamamoto H, Ionov Y, Li Y, Sawai H, Reed JC, Perucho M . 1997 Science 275: 967–969
Smith JR, Carpten JD, Brownstein MJ, Ghosh S, Magnuson VL, Gilbert DA, Trent JM, Collins FS . 1995 Genome Res. 5: 312–317
Souza RF, Appel R, Yin J, Wang S, Smolinski KN, Abraham JM, Zou TT, Shi Y-Q, Lei J, Cottrell J, Cymes K, Biden K, Simms L, Leggett B, Lynch PM, Frazier M, Powell SM, Harpaz N, Sugimura H, Young J, Meltzer SJ . 1996 Nature Genet. 14: 2255–2257
Togo G, Toda N, Kanai F, Kato N, Shiratori Y, Kishi K, Imazeki F, Makuuchi M, Omata M . 1996 Cancer Res. 56: 5620–5623
Wijnen JTh, de Leeuw WJF, van der Klift H, Vasen HFA, Stormoken A, Meijers-Heijboer H, Menko F, Vossen S, Möslein G, Tops C, Bröcker-Vriends A, Wu Y, Hofstra R, Morreau H, Fodde R . 1999 Nature Genet. 23: 142–144
Wu Y, Berends MJW, Mensink RGJ, Kempinga C, Sijmons RH, van der Zee AGJ, Hollema H, Kleibeuker JH, Buys CHCM, Hofstra RMW . 1999 Am. J. Hum. Genet. 65: 1291–1298
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
de Leeuw, W., van Puijenbroek, M., Merx, R. et al. Bias in detection of instability of the (C)8 mononucleotide repeat of MSH6 in tumours from HNPCC patients. Oncogene 20, 6241–6244 (2001). https://doi.org/10.1038/sj.onc.1204795
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1204795
Keywords
This article is cited by
-
Unstable DNA Repair Genes Shaped by Their Own Sequence Modifying Phenotypes
Journal of Molecular Evolution (2010)
-
Frequent mutations in the 3′-untranslated region of IFNGR1 lack functional impairment in microsatellite-unstable colorectal tumours
European Journal of Human Genetics (2008)
-
Genome-wide copy neutral LOH is infrequent in familial and sporadic microsatellite unstable carcinomas
Familial Cancer (2008)
-
HNPCC versus sporadic microsatellite-unstable colon cancers follow different routes toward loss of HLA class I expression
BMC Cancer (2007)
-
High-resolution analysis of HLA class I alterations in colorectal cancer
BMC Cancer (2006)
